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1
Pope, Samuel M. "Specific Role of Eotaxin-1 and Eotaxin-2 in Allergic Pulmonary Eosinophilia". Cincinnati, Ohio : University of Cincinnati, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=ucin1098472372.
Testo completo
2
Benarafa, Charaf. "Equine eotaxin : cloning, expression and biological activity". Thesis, Royal Veterinary College (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.394942.
Testo completo
3
Watanabe, Kimiko. "Eotaxin -1, -2 and -3 generation by different cell types". Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404880.
Testo completo
4
Mariano, Nadia Sabrina. "Estudo da resposta inflamatoria pulmonar alergica em ratos expostos a enterotoxina estafilococica do tipo A (SEA)". [s.n.], 2009. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308954.
Testo completoAbstract (sommario):
Orientadores: Edson Antunes, Ivani Aparecida de SouzaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: O Staphylococcus aureus é um tipo de bactéria gram-positiva que produz e secreta uma série de enterotoxinas com propriedade imunomoduladoras. Entretanto, pouco é conhecido sobre os mecanismos envolvidos na exacerbação do influxo celular observado em indivíduos asmáticos expostos a enterotoxinas estafilocócicas. O objetivo desse trabalho é investigar os efeitos da exposição das vias aéreas à enterotoxina estafilocócica do tipo A (SEA) sobre o recrutamento de leucócitos para o pulmão de ratos sensibilizados e desafiados com ovalbumina (OVA). Em nossos protocolos experimentais, ratos foram expostos à SEA 4 h antes ou 4 h após o desafio antigênico com OVA. O lavado broncoalveolar (LBA), a medula óssea e o tecido pulmonar foram obtidos 24 h após o desafio com OVA. A pré-exposição à SEA aumentou significativamente o número de eosinófilos no LBA e no tecido pulmonar de ratos desafiados com OVA, enquanto que o número de neutrófilos e células mononucleares não foi significativamente alterado. Na medula óssea, a pré-exposição à SEA isoladamente aumentou significativamente o número de eosinófilos, sendo esse aumento potencializado em ratos desafiados com OVA. Por outro lado, a pós-exposição à SEA não afetou o número de eosinófilos, neutrófilos ou células mononucleares observadas no LBA. A pré-exposição ao LPS em animais desafiados com OVA aumentou somente o número de neutrófilos no LBA. No LBA de ratos pré-expostos à SEA e desafiados com OVA, notamos uma elevação significativa nos níveis de TNF-? e eotaxina, mas não de IL-10. Os níveis de eotaxina presentes em sobrenadante de cultura de macrófagos alveolares tratados com SEA in vitro aumentaram cerca de 3 vezes em relação a macrófagos não estimulados com SEA. Concluímos que a pré-exposição (mas não a pós-exposição) das vias aéreas de ratos à SEA aumenta seletivamente o número de eosinófilos presente no LBA, tecido pulmonar e medula óssea de ratos desafiados com OVA por mecanismos que envolvem o aumento na síntese de TNF-? e eotaxina
Abstract: Gram-positive Staphylococcus aureus releases classical enterotoxins which aggravates allergic airway diseases. However, little is known about the mechanisms underlying the cell influx exacerbation in asthmatic individuals under exposure to Staphylococcal enterotoxins. We therefore aimed to investigate the effects of airways exposure to Staphylococcal enterotoxin A (SEA) to pulmonary leukocyte recruitment in rats sensitized and challenged with ovalbumin (OVA). Rats were exposed to SEA at 4 h prior to OVA challenge or at 4 h post-OVA challenge. Bronchoalveolar lavage (BAL) fluid, bone marrow and lung tissue were obtained at 24 h after OVA challenge. Preexposure to SEA markedly enhanced the eosinophil counts in both BAL fluid and pulmonary tissue in OVA-challenged rats, whereas neutrophil and mononuclear cell counts remained unchanged. In bone marrow, pre-exposure to SEA alone significantly increased the number of eosinophils, and that was further increased in OVA-challenged rats. Exposure to SEA post-OVA challenge did not affect the number of eosinophils, neutrophils and mononuclear cells in BAL fluid. Pre-exposure to the endotoxin lipopolyssacharide (LPS) in OVA-challenged animals rather enhanced the neutrophil number in BAL fluid. In rats pre-exposed to SEA and OVA-challenged, a marked elevation in the levels of TNF-? and eotaxin (but not of IL-10) in BAL fluid was observed. The eotaxin levels increased by about of 3-fold in alveolar macrophages treated with SEA in vitro. In conclusion, airways pre-exposure to SEA (but not the postexposition) causes a selective increase in eosinophil number in BAL fluid, lung tissue and bone marrow of OVA-challenged rats by mechanisms involving enhancement of TNF-? and eotaxin synthesis
Mestrado
Farmacologia
Mestre em Farmacologia
5
Bodman, Lee Graham. "The effect of glycosylation on the biological activity of eotaxin and related chemokines". Thesis, Imperial College London, 2004. http://hdl.handle.net/10044/1/11889.
Testo completo
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Ghaffar, Omar. "Constitutive and cytokine-stimulated expression of eotaxin by human airway smooth muscle cells". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0024/MQ50776.pdf.
Testo completo
7
Menzies-Gow, Andrew Neil. "The roles of interleukin-5 and eotaxin in oesinophil recruitment, maturation and activation". Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.429161.
Testo completo
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Kirchem, Antje. "Investigation of the signalling pathways coupled to the eotaxin receptor CCR3 in human eosinophils". Thesis, Imperial College London, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406094.
Testo completo
9
Konikoff, Michael R. "Non-Invasive Biomarkers of Eosinophilic Esophagitis: Blood Eosinophil Level, Eosinophil-Derived Neurotoxin, and Eotaxin-3". Cincinnati, Ohio : University of Cincinnati, 2006. http://www.ohiolink.edu/etd/view.cgi?acc_num=ucin1148043525.
Testo completoAbstract (sommario):
Thesis (M.S.)--University of Cincinnati, 2006.Advisor: Dr. James E. Heubi. Title from electronic thesis title page (viewed June 3, 2009). Includes abstract. Keywords: Eosinophilic esophagitis; biomarker; eosinophil; eosinophil-derived neurotoxin; eotaxin-3. Includes bibliographical references.
10
Lieschke, Simone [Verfasser]. "Untersuchung der Rolle von Eotaxin-1 nach ischämischem Schlaganfall im Mausmodell: Neuroprotektion, Neuroregeneration oder destruktiv-proinflammatorische Rolle? / Simone Lieschke". Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2021. http://d-nb.info/1232492825/34.
Testo completo
11
Waddell, Amanda B. "Role of macrophages and eosinophils in inflammatory bowel diseases". University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1327949608.
Testo completo
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Stenin, Igor [Verfasser]. "Die Freisetzung von IL-4, IL-13, IL-33, sST2 und Eotaxin 3 nach nasaler Allergenprovokation bei Probanden mit allergischer Rhinitis / Igor Stenin". Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2016. http://d-nb.info/1100688846/34.
Testo completo
13
Kobayashi, Yoshiki. "Physiological level of 15-deoxy-Δ[12,14]-prostaglandin J2 prime eotaxin-induced chemotaxis on human eosinophils through peroxisome proliferator-activated receptor-γ ligation". Kyoto University, 2007. http://hdl.handle.net/2433/135911.
Testo completo
14
Carvalho, Gerson da Silva. "Caracterizaçāo das citocinas na doença de Machado Joseph". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/150989.
Testo completoAbstract (sommario):
A Doença de Machado Joseph(DMJ) é uma doença genética autossômica dominante de início na vida adulta que afeta a coordenação motora e cursa com sintomas neurodegenerativos. É causada por uma expansão da repetição CAG no gene ATXN3. Há várias hipóteses a respeito da sua fisiopatogenia, e uma delas envolve a resposta inflamatória. O objetivo deste estudo foi descrever as concentrações séricas das citocinas em indivíduos sintomáticos, assintomáticos e compará-los com os controles saudáveis. Após a confirmação molecular dos pacientes e controles pareados por sexo e idade, os indivíduos foram convidados a participar do estudo. A idade de início e a duração da doença foram obtidas, e as escalas clínicas Scale for the Assessment and Rating of Ataxia (SARA), Neurological Examination Score for Spinocerebellar Ataxias (NESSCA), SCA Functional Index (SCAFI), and Composite Cerebellar Functional Score (CCFS), aplicadas. O soro dos indivíduos foi coletado e um painel de citocina foi realizado, incluindo a Eotaxina, GM-CSF, IFN-a, IFN-γ, IL-1b, IL-1Ra, IL-2, IL-2R, IL-4, IL- 5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, IP-10, MCP-1, MIG, MIP1a, MIP1b, RANTES e O TNF-a. Entre os indivíduos sintomáticos, o painel foi repetido após 90 e 360 dias. O perfil das citocinas no baseline foi estudado por análise discriminante. Aquelas que apresentaram alterações relevantes entre os grupos tiveram seus níveis sérico reavaliados após 90 e 360 dias e estes dados foram avaliados pela equação de estimação generalizada (GEE). Sessenta e seis sintomáticos, 13 assintomáticos e 43 controles foram estudados. Quando comparados os sintomáticos e assintomáticos com seus respectivos controles saudáveis, não se observou diferenças nos padrões das citocinas. No entanto, apenas uma citocina teve destaque: os níveis séricos de Eotaxina foram significativamente mais elevados em assintomáticos (p = 0,001, ANCOVA) e entre os sintomáticos seus níveis foram menores após 360 dias do que naquelas obtidas no início do estudo (p = 0,039, GEE). A idade, a duração da doença, a expansão CAG, e as escalas NESSCA e SARA não se correlacionaram com os níveis das citocinas. O padrão relativamente benigno de citocinas em portadores sintomáticos sugere que a ativação do micróglia não seja primordial na DMJ. Entretanto, os níveis de eotaxina, um peptídeo secretado por astrócitos para repelir as células imunes circulantes, foram elevados no grupo assintomático, o que sugere que uma resposta específica destas células pode estar relacionada com a ausência de sintomas e/ou que a perda de astrócitos estaria relacionada à progressão da doença em DMJ.Machado Joseph Disease (MJD) is an autosomal dominant genetic disease of adulthood which affects motor coordination and progresses with neurodegenerative symptoms. It is caused by an expansion of the CAG repeat at ATXN3 gene. There are several hypotheses about its pathogenesis, and one of them involves the inflammatory response. The aim of the present study is to describe the serum concentrations of a broad spectrum of cytokines in symptomatic and asymptomatic carriers of Machado Joseph disease (SCA3/MJD) CAG expansions. Molecularly confirmed carriers and controls were studied. Age at onset, disease duration, and clinical scales Scale for the Assessment and Rating of Ataxia (SARA), Neurological Examination Score for Spinocerebellar Ataxias (NESSCA), SCA Functional Index (SCAFI), and Composite Cerebellar Functional Score (CCFS) were obtained from the symptomatic carriers. Serum was obtained from all individuals and a cytokine panel consisted of eotaxin, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-α, IFN-γ, interleukin (IL)-1β, IL-1RA, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL- 12, IL-13, IL-15, IL-17, interferon gamma-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, monokine induced by gamma interferon (MIG), macrophage inflammatory protein (MIP)-a, MIP-b, regulated on activation, normal T cell expressed and secreted (RANTES) and tumor necrosis factor (TNF)-α was analyzed. In a subgroup of symptomatic carriers, the cytokine panel was repeated after 90 and 360 days. Cytokine distribution among groups was studied by discriminant analysis; changes in serum levels after 90 and 360 days were studied by generalized estimation equation. Sixty-six symptomatic carriers, 13 asymptomatic carriers, and 43 controls were studied. No differences in cytokine patterns were found between controls and carriers of the CAG expansions or between controls and symptomatic carriers only. In contrast, eotaxin concentrations were significantly higher in asymptomatic than in symptomatic carriers or in controls (p = 0.001, ANCOVA). Eotaxin did not correlate with age, disease duration, CAG expansion, NESSCA score, and SARA score. Among symptomatic carriers, eotaxin dropped after 360 days (p = 0.039, GEE). SCA3/ MJD patients presented a benign pattern of serum cytokines. In contrast, levels of eotaxin, a peptide secreted by astrocytes, were elevated in the asymptomatic carriers, suggesting that a specific response of these cells can be related to symptom progression, in SCA3/MJD.
15
Su, Yung-Chang University of New South Wales & Garvan Institute of Medical Research St Vincent's Clinical School UNSW. "Immune regulation in mouse models of allergic asthma". Awarded by:University of New South Wales & Garvan Institute of Medical Research. St. Vincent's Clinical School, 2006. http://handle.unsw.edu.au/1959.4/26978.
Testo completoAbstract (sommario):
Allergic asthma is an immunological disease, mediated by CD4+ Th2 cells, and its prevalence has increased over recent decades. Features of allergic asthma include airway hyperresponsiveness (AHR), airway eosinophilia, excessive airway mucus production, and increased IgE and Th2 cytokine levels. Airway remodeling with pulmonary fibrosis is noted in the progress of asthma. In this thesis, a murine model of allergic asthma was used to investigate the effect of cyclophosphamide (CY) on asthma and the involvement of regulatory T cells (Treg), and the role of Granulocyte-macrophage colony stimulating-factor (GM-CSF) in allergic asthma by using GM-CSF knockout mice. CY is a cytotoxic agent, which paradoxically augments several immune responses. The first part of this thesis was aimed to study the effects of CY in a murine model of allergic airway inflammation. BALB/c mice were immunized with ovalbumin (OVA) on days 0 and 14, and challenged with aerosolized OVA from days 21 to 27. Some mice additionally received CY on days -2 and 12. In the CY-treated animals, pronounced worsening of inflammatory features was noted, including increases in eosinophil infiltration, epithelial thickness, mucus occlusion and eosinophil numbers in bronchoalveolar lavage fluid (BALF). Increased total and OVA-specific serum IgE were also noted in the CY-treated animals. In cell cultures from peritracheal lymph nodes, the Th2 cytokines IL-4 and IL-5 were elevated in animals treated with CY. It was hypothesized that the effects of CY could be caused by reduced immunosuppression mediated by Treg. mRNA expression of the immunosuppressive cytokines IL-10 and TGF-beta was reduced in the lungs of CY-treated mice. The expression of FoxP3, a marker of naturally occurring Treg, was significantly reduced in spleens, thymuses and peritracheal lymph nodes after the second injection of CY, and in the lung tissue after allergen challenge in CY-treated mice. Furthermore, lung IL-10-producing CD4+ T cells and CTLA-4+-bearing CD4+ T cells were reduced after allergen aerosol challenge in CY-treated mice. Thus CY worsened the features of allergic pulmonary inflammation in this model, in association with increased production of IgE and Th2 cytokines. The reduction in expression of FoxP3 and immunosuppressive cytokines by CY suggests that toxicity to Treg may contribute to the increased inflammation. GM-CSF plays a role in the growth, development, and maturation of bone marrow hemopoietic cells into mature blood cells, and has been proposed to be involved in potentiating the function of inflammatory cells in allergic inflammation. In the second part of this thesis, GM-CSF knockout (KO) mice were used to investigate the role of GM-CSF. In allergic KO mice, airway eosinophils were only shown in the perivascular, but not peribronchial areas in the lung, compared to the allergic wild-type (WT) mice in which eosinophil infiltration appeared in both areas. Eosinophil numbers were drastically reduced in the bronchoalveolar lavage fluid (BALF) of KO mice. IL-5 production in the lung tissue and BALF in allergic KO mice was reduced; similar results were also found in peritracheal draining lymph nodes after in vitro stimulation assays. However, IL-4 and IL-13 production, airway hyperresponsiveness (AHR), and serum IgE production were not affected in allergic KO mice. Surprisingly, lung IFN-gamma mRNA and BALF levels were increased in allergic KO mice. Lung mRNA levels of CCR3, a key chemokine receptor on eosinophils, were significantly reduced in allergic KO mice, whereas expression of the chemokines eotaxin and RANTES were at similar levels in allergic KO and WT mice. Lung mRNA levels of the IFN-gamma-inducible chemokines Mig (CXCL9) and IP-10 (CXCL10), which are antagonists of CCR3, and their receptor CXCR3 were increased in allergic KO mice, compared with allergic WT mice. Data obtained from flow cytometry showed more eosinophils survived in the lung of WT mice than KO mice. Another allergy model, a peritoneal allergy model was performed to investigate inflammation in a different model. Leukocyte subpopulations such as neutrophils, eosinophils, macrophages, and lymphocytes were reduced in the peritoneal lavage fluid of allergic KO mice. The findings revealed that GM-CSF is essential for IL-5 production, pulmonary airway eosinophilia and eosinophil survival. In the absence of GM-CSF, over-production of IFN-???? may induce chemokines, including Mig and IP-10, which are antagonists for CCR3 and may reduce airway eosinophil infiltration. In this thesis, a murine model of allergic asthma has been used to obtain novel findings on the regulation of allergic inflammation. The results with CY are relevant to the treatment of asthma patients with CY and other cytotoxic agents. The findings in the GM-CSF KO mice suggest that GM-CSF is a potential therapeutic target in asthma, and that in assessment of new therapeutic agents for asthma, effects on GM-CSF should be considered.
16
Carmo, Lívia Andressa Silva do. "Avaliação ultraestrutural da mobilização do CD63 em eosinófilos humanos estimulados com eotaxina ou TNF-\03B1". reponame:Repositório Institucional da FIOCRUZ, 2014. https://www.arca.fiocruz.br/handle/icict/12865.
Testo completoAbstract (sommario):
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Previous issue date: 2016-01-13Os eosinófilos são leucócitos que estão envolvidos em respostas inflamatórias, alérgicas e imunoreguladoras, através da secreção de proteínas catiônicas e citocinas armazenadas em seus grânulos específicos. Os mecanismos de secreção podem ocorrer por: (i) desgranulação por piecemeal (PMD), caraterizada pelo transporte mediado por vesículas que brotam dos grânulos e levam os produtos até a superfície celular; (ii) exocitose clássica, caracterizada pela fusão dos grânulos com a membrana plasmática e (iii) citólise, quando os grânulos são liberados após lise celular. O CD63 é uma molécula da família das tetraspaninas que parece atuar como facilitador na secreção de mediadores da inflamação. Entretanto, não existem estudos ultraestruturais que demonstrem a associação de CD63 com processos de secreção de eosinófilos. Este trabalho teve por objetivo investigar a mobilização de CD63 e sua correlação com mecanismos de secreção em eosinófilos humanos estimulados com mediadores inflamatórios (eotaxina e fator de necrose tumoral -TNF-\03B1). A expressão de CD63 foi investigada na superfície celular através de imunofluorescência e em compartimentos subcelulares através de imunomarcação pre-embedding por microscopia eletrônica de transmissão que permite melhor preservação antigênica e os anticorpos mostram ótimo acesso a microdomínios celulares com partículas de ouro (1.4 nm) conjugadas a anticorpos secundários A imunofluorescência mostrou elevada expressão de CD63 na superfície celular, mas com padrões diferentes dependendo do estímulo. Enquanto a eotaxina induziu imunomarcação pontual, a expressão de CD63, induzida por TNF- \03B1, mostrou-se de maneira difusa, indicando a ocorrência de processos de secreção diferentes. As análises ultraestruturais revelaram que a eotaxina induziu PMD, enquanto o TNF-\03B1 desencadeou exocitose clássica. O CD63 foi detectado principalmente nos grânulos de secreção. As análises quantitativas mostraram que nos grupos estimulados ocorreu aumento significativo do número de grânulos CD63- positivos em comparação com o grupo controle não estimulado. Além disso, 89,94 % dos grânulos sofrendo PMD (grupo eotaxina) e 84,73% dos grânulos sofrendo fusão (grupo TNF-\03B1) eram positivos para CD63. A marcação para CD63 foi também documentada em endossomos e em vesículas, incluindo vesículas tubulares típicas de eosinófilos (Eosinophil Sombrero Vesicles \2013 EoSVs), envolvidas no transporte de moléculas dos grânulos. Em conjunto, nossos dados demonstraram, pela primeira vez, que CD63 é um marcador tanto de grânulos de secreção como de processos secretores envolvidos na liberação de produtos de eosinófilos. Isto é importante para o entendimento de mecanismos de liberação de mediadores imunes durante respostas de eosinófilos a doenças alérgicas e inflamatórias
Eosinophils are leukocytes involved with inflammatory, allergic and immmunoregulatory responses through the secretion of granule-stored cationic proteins and cytokines. Secretion can occur by: (i) piecemeal degranulation (PMD), characterized by vesicle-mediated transport of products from granules to cell surface; (ii) classical exocytosis, characterized by granule fusion with the plasma membrane e (iii) cytolysis, in which the granule content is released after cell lysis. CD63 is a tetraspanin family molecule which seems to act as a facilitator during secretion of inflammatory mediators. However, there are no ultrastructural studies demonstrating association of CD63 with secretory processes of eosinophils. The goal of this work was to investigate the mobilization of CD63 and its association with mechanisms of secretion in human eosinophils stimulated with inflammatory mediators (eotaxin and tumoral necrosis factor-TNF-α). Expression of CD63 was investigated at the cell surface using immunofluorescence technique and in subcellular compartments by pre-embedding ultrastructural immunolabeling which enables better antigenic preservation. Optimal access of antibodies to cellular microdomains was achieved with gold particles (1.4 nm) conjugated with secondary antibodies. Immunofluorescence showed high CD63 expression at cell surface, but with different profiles, depending on the stimulus. While eotaxin induced a punctual immunolabeling, expression of CD63, induced by TNF-α, was more diffuse, indicating occurrence of different secretory processes. Ultrastructural analyses revealed that eotaxin induced PMD, while TNF-α led to classical exocytosis. CD63 was detected mainly on secretory granules. Quantitative analyses showed a significant increase of the numbers of CD63-positive granules compared to the unstimulated, control group. Moreover, 89.94 % of the granules undergoing PMD (eotaxin group) and 84.73% of the granules in fusion process (TNF-α group) were positive for CD63. CD63 labeling was also documented in endosomes and vesicles, including tubular vesicles typical of eosinophils (Eosinophil Sombrero Vesicles – EoSVs), involved in the transport of granule molecules. Altogether, our data demonstrated, for the first time, that CD63 is a marker for secretory granules as well as for secretory processes involved with the release of products from eosinophils. This is important for understanding mechanisms of secretion of immune mediators during inflammatory responses of eosinophils to allergic and inflammatory diseases.
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Lintomen, Leticia. "Estudo da inibição do oxido nitrico sobre funções de eosinofilos humanos estimulados com eotaxina e RANTES in vitro". [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308929.
Testo completoAbstract (sommario):
Orientador: Edson ArantesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Os eosinófilos participam da patogênese de várias doenças inflamatórias, incluindo infecções parasíticas e doenças alérgicas. Dentre as doenças alérgicas, a eosinofilia tem presença marcante na asma. Atualmente, a asma afeta 300 milhões de indivíduos no mundo, sendo considerada um problema de saúde pública mundial. A asma é uma doença inflamatória crônica que envolve interações entre fatores externos e genéticos, e tem como características principais a inflamação pulmonar e a hiperresponsividade brônquica. O recrutamento de eosinófilos para as vias aeríferas contribui para o caráter crônico da asma. A migração de eosinófilos para o tecido inflamado é um processo complexo, que é regulado por numerosos fatores, incluindo citocinas, quimiocinas, óxido nítrico (NO) e interações de moléculas de adesão. Estudos prévios investigaram as interações funcionais entre NO e CC-quimiocinas. Young e colaboradores (1999) mostraram que o número de eosinófilos no lavado broncoalveolar (LBA) de macacos desafiados está marcadamente aumentado 24 horas após o desafio, e que este aumento é acompanhado de altos níveis de NO no ar exalado e de eotaxina no LBA. Em pacientes com rinite, a eotaxina aumentou o número de eosinófilos no fluido do lavado nasal e também os níveis de NO nasal (Hanazawa et al., 1999). Em contraste, em modelos murinos de asma a inibição seletiva da NOS induzível resultou na redução da migração eosinofílica para os pulmões (Feder et al., 1997; Iijima et al., 2001), que estava associada com o aumento da expressão da CC-quimiocina proteína quimiotática para monócito-1 (MCP-1) no tecido pulmonar (Trifilieff et al., 2000). Além disso, NO (ou doadores de NO) também são capazes de inibir a produção de RANTES (Frank et al., 2000). O NO via formação de peroxinitrito (ONOO-) também pode reduzir a migração de eosinófilos induzida por eotaxina (Sato et al., 2000). Entretanto, o papel modulatório do NO nas funções do eosinófilo mediadas por CC-quimiocinas ainda permanece contraditório. Portanto, o presente trabalho investigou o efeito modulatório do NO na adesão aumentada, quimiotaxia e desgranulação do eosinófilo induzidas pelas Ccquimiocinas eotaxina e RANTES in vitro, e a expressão de VLA-4 e Mac-1 na superfície do eosinófilo. Nós realizamos ensaios funcionais (adesão e desgranulação), análise da expressão de moléculas de adesão por citometria de fluxo (VLA-4 e Mac-1) e a investigação de resíduos de tirosina nitrada para avaliar interações do NO com CC-quimiocinas em eosinófilos humanos. Os ensaios de MTT mostraram que as incubações de eosinófilos por 2, 3, ou 4 horas com eotaxina (10, 100 e 1000 ng/ml) ou RANTES (10, 100 e 1000 ng/ml) não afetam a viabilidade celular e, em determinadas condições, até promovem a ativação das células. Os resultados de adesão à fibronectina mostraram que a eotaxina (10, 100 e 1000 ng/ml) ou RANTES (10, 100 e 1000 ng/ml) não aumentam a adesão de eosinófilos em períodos de incubação de 2 e 3 horas. Entretanto, a incubação de eosinófilos por 4 horas com eotaxina ou RANTES aumentou significativamente a adesão à fibronectina. O L-NAME (0.1 mM), individualmente, aumentou significativamente a adesão de eosinófilos à fibronectina; porém a co-incubação de L-NAME com eotaxina (ou RANTES) não afetou a adesão observada com cada agente isoladamente. Além disso, a expressão de VLA-4 e de Mac-1 não foi modificada em nenhuma das condições experimentais testadas. Eotaxina e RANTES também não foram capazes de aumentar os níveis de GMPc nos eosinófilos, em condições onde o SNP (0.1 mM), usado como controle positivo, aumentou significativamente os níveis desse segundo mensageiro. Além disso, eosinófilos tratados com L-NAME, eotaxina e RANTES, individualmente, foram capazes de desgranular estas células, mas a co-incubação de LNAME com eotaxina (ou RANTES), não alterou esta resposta. Os resultados de quimiotaxia mostraram migração significativa de eosinófilos (tratados ou não com LNAME) em resposta à eotaxina ou RANTES. Os resultados obtidos de Western blotting para 3-nitrotirosina mostraram ausência de proteínas nitradas nos eosinófilos de indivíduos sadios ou asmáticos. No conjunto, nossos resultados mostram que, nas condições experimentais estabelecidas, o NO não modula adesão, migração e desgranulação em eosinófilos estimulados com eotaxina ou RANTES
Abstract: Eosinophils participate in the pathogenesis of many inflammatory diseases, including parasitic infections and allergic diseases. Of the allergic diseases, asthma is characterized by eosinophilia. Currently, asthma affects 300 million people in world, and is an important public health problem. Asthma is an inflammatory chronic disease that involves interactions between external and genetic factors, and has lung inflammation and bronchial hyperresponsiveness as major features. The recruitment of eosinophils into airways contributes to the asthma chronic character. The eosinophil migration to inflamed tissue is a complex process regulated by several factors, including cytokines, chemokines, nitric oxide (NO) and adhesion molecule interactions. Previous studies have investigated the functional interactions between NO and CC-chemokines. Young et al. (1999) showed that the number of eosinophils in the bronchoalveolar lavage (BAL) fluid of challenged monkeys is markedly increased at 24 h post-challenge, accompanied by higher levels of both exhaled NO and eotaxin in BAL fluid. In rhinitis patients, eotaxin increased the number of eosinophils in the nasal lavage fluid, and that was also accompanied by elevated nasal NO levels (Hanazawa et al., 1999). In contrast, in murine models of asthma, selective inhibition of inducible NOS resulted in a reduction in pulmonary eosinophil migration (Feder et al., 1997; Iijima et al., 2001), with an increased expression of the CC-chemokine monocyte chemoattractant protein-1 (MCP-1) in the lung tissue (Trifilieff et al., 2000). Moreover, NO (or NO donors) have also been shown to inhibit the production of RANTES (Frank et al., 2000). Nitric oxide via peroxynitrite (ONOO-) formation is reported to reduce eotaxin-induced eosinophil migration (Sato et al., 2000). However, the modulatory role of NO in the CC-chemokines-mediated eosinophil functions is still not well understood. Therefore, the present study was designed to investigate the modulatory effect of NO in the enhanced eosinophil adhesion, chemotaxis and degranulation induced by the Ccchemokines eotaxin and RANTES in vitro, and the expression of VLA-4 and Mac-1 on the eosinophil surface. We therefore carried out functional assays (adhesion and degranulation), flow cytometry analysis of adhesion molecules (VLA-4 and Mac-1 expression) and investigation of tyrosine nitration to evaluate the interactions between NO and CC-chemokines in human eosinophils. MTT assays showed that incubation of eosinophils for 2, 3 or 4 hours with eotaxin (10, 100 and 1000 ng/ml) or RANTES (10, 100 and 1000 ng/ml) did not affect cellular viability and, in some conditions, even caused cellular activation. The results of adhesion to fibronectin showed that eotaxin (10, 100 and 1000 ng/ml) or RANTES (10, 100 and 1000 ng/ml) did not increase eosinophil adhesion at 2 or 3 hours of incubation. Nevertheless, the incubation of eosinophils for 4 hours with eotaxin or RANTES significantly increased adhesion to fibronectin. L-NAME (0.1 mM), alone, significantly increased eosinophil adhesion to fibronectin; however the co-incubation of L-NAME with eotaxin (or RANTES) did not affect the adhesion of each agent. Moreover, expression of VLA-4 and Mac-1 were not modified by any of the experimental conditions. Eotaxin and RANTES did not increase eosinophil cGMP levels under the same conditions in which SNP (0.1mM), used as a positive control, significantly increased the levels of this second messenger. Furthermore, eosinophils treated with L-NAME, eotaxin and RANTES, alone, demonstrated degranulation, however the co-incubation of eosinophils with L-NAME and eotaxin (or RANTES) did not alter this response. Chemotaxis assays showed a significant eosinophil (treated or not with L-NAME) migration in response to eotaxin or RANTES. Western blotting for 3-nitrotyrosine-3 showed a lack of nitrated proteins in eosinophils from healthy or asthmatic donors. Taken together, results show that, under the experimental conditions established, NO does not modulate adhesion, migration and degranulation in eotaxin or RANTES-stimulated eosinophils
Doutorado
Doutor em Farmacologia
18
Costa, Gislaine Gomes da. "Avaliação da habilidade quimiotaxica e da adesão de eosinofilos de pacientes com rinite alergica : efeito da eotaxina e interleucina-5". [s.n.], 2004. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308952.
Testo completoAbstract (sommario):
Orientador: Edson AntunesDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Neste estudo, investigamos se a IL-5, a eotaxina e a dexametasona modulam a migração e adesão de eosinófilos obtidos de indivíduos sadios e de pacientes com rinite alérgica. O ensaio de quimiotaxia e de adesão foi realizado com eosinófilos de sangue periférico usando-se sistema imunomagnético de separação celular. Para os ensaios de quimiotaxia, foram utilizadas placas ChemoTx-5, e para os ensaios de adesão, placas de adesão recobertas com fibronectina. Em ambos os ensaios, a medida da absorbância (490 nM) da peroxidase eosinofílica foi utilizada como índice de eosinófilos migrados ou aderidos. O PAF (10~ M) induziu quimiotaxia de mesma magnitude em eosinófilos de indivíduos sadios e de pacientes com rinite. A IL-5 (0,25 nglml) aumentou significativamente a quimiotaxia de eosinófilos induzida pelo PAF; porém, o aumento observado em eosinófilos de pacientes com rinite alérgica foi 65% maior (p<0,001) do que de indivíduos sadios. A eotaxina (100 nglml) não alterou a resposta quimiotáxica do PAF em nenhum dos grupos estudados. A dexametasona (100 J.1g/ml)reduziu significativamente a quimiotaxia, tanto no grupo de indivíduos sadios, como no de pacientes com rinite alérgica. A IL-5 (0,25 ng/ml) induziu resposta quimiotáxica significativamente maior em eosinófilos de pacientes com rinite, em comparação com eosinófilos de indivíduos sadios. A resposta quimiotáxica à IL-5 não foi modificada pela eotaxina (100 ng/ml) em eosinófilos de indivíduos sadios, mas foi marcantemente reduzida em eosinófilos de pacientes com rinite alérgica. A eotaxina (100 nglml) induziu resposta quimiotáxica significativamente maior em eosinófilos de pacientes com rinite, em comparação com eosinófilos de indivíduos sadios. A resposta quimiotáxica à eotaxina foi potencializada pela IL-5 (100 ng/ml)em eosinófilos de indivíduos sadios e de pacientes com rinite alérgica. Entretanto, o aumento observado nos eosinófilos de pacientes com nnite alérgica foi significativamente maior do que de indivíduos sadios. Em placas recobertas com fibronectina (10 J.1g1m,l) ligante oposto da molécula de adesão VLA-4, estudamos a adesão dos eosinófilos. A adesão espontânea foi maior com eosinófilos de pacientes com rinitealérgica do que de indivíduos sadios. A incubação dos eosinófilos com eotaxina (100 nglml) ou IL-5 (0,25 ng/ml) não modificou a adesão dos eosinófilos em nenhum dos grupos estudados. A incubação com dexametasona (100 J.1g1ml) reduziu significativamente a adesão celular em ambos os grupos experimentais. Nossos resultados mostram que eosinófilos de pacientes com rinite alérgica estão pré-ativados. Isto pode ser devido à exposição na circulação à IL-5, que leva ao aumento da expressão elou função da molécula de adesão VLA-4 e, conseqüentemente,de sua migração
Abstract: In this study, we tested whether IL-5, eotaxin and dexamethasone modulate the adhesion and migration of eosinophils obtained trom allergic rhinitis subjects, in comparison with healty individuais. The chemotaxis and adhesion assays were performed with eosinophils isolated from peripheral blood using an imunomagnetic cell separator. ChemoTx-5 plates were used for the chemotaxis assays, whereas fibronectin-coated plates were used for the adhesion assays. For both assays, measurement of eosinophil peroxidase activity was used as marker for migrated or adhered eosinophils. Platelet-activated factor (PAF; 10-8 M) induced a significant eosinophil chemotaxis in both studied groups. Interleukin-5 (IL-5, 0.25 nglml) significantly increased the PAF-induced chemotaxis in eosinophils trom both healthy individuais and rhinitis subjects. However, the increase in rhinitis subjects eosinophils was 65% higher (p<0.001) compared with healthy individuais eosinophils. Eotaxin (100 ng/ml) did not alter the PAF-induced eosinophil chemotaxis in either groups studied. Dexamethasone (100 Ilg/ml) significantly reduced PAF-induced chemotaxis in cells trom both groups. Interleukin-5 (0.25 nglm!) induced a higher chemotactic response in eosinophils trom rhinitis subjects compared with healthy individuais. Eotaxin (100 ng/ml) had no effect on IL-5-induced eosinophil chemotaxis in healthy individuais, but prevented the increase in eosinophil chemotaxis induced by IL-5 in rhinitis subjects. Eotaxin (100 ng/ml) induced a higher chemotactic response in eosinophils trom rhinitis subjects compared with healthy individuais. Eotaxin-induced eosinophil chemotaxis was significantly enhanced by IL-5 (0.25 nglml) in both group studied, but this enhancement was higher in eosinophils trom rhinitis subjects. In plated coated with fibronectin (an opposite ligand for VLA-4) we studied the eosinophil adhesion. The basal (spontaneous) cell adhesion was siginificantly higher (p<0.05) using eosinophils from rhinitis subjects compared with those trom healthy individuais. However, the pattem of cell adhesion in both groups was not significantlyaffectedby eotaxin (100 ng/ml) or IL-5 (0.25 nglm!). Dexamethasone (100 Ilg/ml) significantly reduced the eosinophil adhesion in cells from both studied groups. Ours results indicate that eosinophils trom rhinitissubjects are found primed, and that can be due to previous exposition to IL-5 while in peripheral blood. It is likelythat IL-5 increases the expression andlor function01adhesion molecule VLA- 4 in eosinophils leading consequently to an enhanced cell chemotaxis
Mestrado
Farmacologia
Mestre em Farmacologia
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Krisiukėnienė, Algirda. "Rūkymo sąlygoti imuninio atsako ypatumai sergant astma". Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2009. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2009~D_20090604_110354-67472.
Testo completoAbstract (sommario):
Astma-lėtinė kvėpavimo takų liga, pasireiškianti dusulio ar kosulio epizodais bei padidėjusiu bronchų reaktyvumu. Eksperimentiniai bei klinikiniai tyrimai parodė, kad lėtinis neinfekcinis kvėpavimo takų uždegimas- svarbiausia astmos patogenezės grandis, lemianti šios ligos klinikinę eigą, sunkumą bei skiriamo gydymo efektyvumą. Nėra aišku, ar alerginė bei nealerginė astma skiriasi ne tik klinikiniu pasireiškimu, bet ir patomorfologiniais bei patofiziologiniai kvėpavimo takų pakitimais. Rūkymas- svarbus veiksnys, sukeliantis reikšmingus pokyčius kvėpavimo takų gleivinėje. Tačiau kaip rūkymas įtakoja lėtinį neinfekcinį kvėpavimo takų uždegimą ir ar skiriasi rūkymo poveikis sergant fenotipiškai skirtingomis astmos formomis- nėra žinoma. Todėl šio tyrimo tikslas- nustatyti rūkymo sąlygotus imuninio atsako ypatumus sergant alergine ir nealergine astma. Ištirti alergine ir nealergine astma sergantys pacientai, kurie pagal rūkymo įpročius suskirstyti į grupes: rūkorius ir nerūkančiuosius. Įvertinti rūkymo sąlygoti skreplių, bronchoalveolinio lavažo skysčio ląstelių sudėties skirtumai, eotaksinų, IL-5 bei IL-9 koncentracijų ypatumai, jų ryšys su svarbiausiais klinikiniais pacientų duomenimis. Nustatyta, kad alerginė ir nealerginė astma skiriasi patofiziologinėmis savybėmis, o rūkymas sukelia nevienodus imuninių lėtinio kvėpavimo takų uždegimo žymenų pakitimus pacientams, sergantiems skirtingomis astmos formomis.Asthma is a chronic disorder of the airways, which is characterized by the presence of chronic airway inflammation. Experimental and clinical studies have showed that chronic airway inflammation is the most important part of asthma pathogenesis, which determines the clinical picture and severity of this disease. The data about differences and similarities of allergic and non-allergic asthma are questionable. It was considered that smoking might cause significant changes of bronchial mucosa. It is unclear whether smoking impairs immune response in patients with allergic and non-allergic asthma similarly. The aim of this study was to evaluate tobacco smoke-induced features of immune response in patients with allergic and non-allergic asthma. Subjects, with allergic and non-allergic asthma were investigated. According to their smoking habits, patients were divided into the groups: smokers and non-smokers. Tobacco smoke-induced changes of sputum and BAL fluid cellular composition were evaluated and features of inflammatory mediators (eotaxins, IL-5 and IL-9) were investigated. This study showed pathomorphological and pathophysiological differences between allergic and non-allergic asthma. Smoking impairs lung function and changes the pattern of chronic airway inflammation by decreasing production of cytokines and increasing production of chemokines.
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Castro, Mirian Cabral Moreira de. "Perfil de expressão gênica de il-5, gm-csf, tgf-1, eotaxina na poliposenasossinusal eosinofílica pós-cirurgia endoscópica e efeito da mitomicina c tópica". Universidade Federal de Minas Gerais, 2010. http://hdl.handle.net/1843/BUOS-8GRNKX.
Testo completoAbstract (sommario):
Nasosinusal polyposis is a degeneration of the mucosa of the nose and paranasal sinuses with the participation of several inflammatory cytokines. Objective: To compare the differences in the expression of inflammatory genes in eosinophilic nasosinusal polyposis prior and after the topical application of Mitomycin C in the maxillary sinus, and to relate it to their expression in normal tissue. Casuistic and Method: twenty patients with nasosinusal polyposis and six patients with pituitary adenoma were selected and underwent endoscopic surgical treatment. Maxillary sinus mucosa was biopsied at surgery and the left maxillary sinus was submitted to topical application of 3 ml of Mitomycin C O.5 mg/ml for 5 minutes. In the 21st day after surgery a new biopsy was collected from the maxillary sinuses. In the six patients who underwent transsphenoidal surgery for removal of pituitary tumors a biopsy of the normal mucosa of the sphenoid sinus was carried out. The samples were analyzed through RT-qPCR for the expression of IL5, eotaxin, granulocyte macrophage colony stimulating factor and that also transforming growth factor beta-1. Results: It was observed, in the diseased mucosa, an asymmetric distribution for the values of the cytokines. The values of eotaxin diminished after treatment. In the left maxillary sinus, the expression of IL5 was greater in the trans-operatory period (prior to the application of Mitomycin C) compared to normal tissue and to the 21st day after the application of the medication. Conclusion: There was indication of the action of Mitomycin C in the subexpression of IL5. It was also observed the recommendation of the benefit of surgery and corticoid for eotaxin. The expression of cytokines had asymmetrical values, and increased in relation to normal tissue except for beta-1 growth factor.A polipose nasossinusal (PNSE) é uma degeneração da mucosa do nariz e seios paranasais, com participação de várias citocinas inflamatórias. Objetivo: comparar as diferenças de expressão de genes inflamatórios na PNSE pré e pósaplicação tópica de mitomicina C nos seios maxilares e relacioná-las com a expressão dos tecidos normais. Casuística e métodos: foram selecionados 20 pacientes com PNSE e seis com adenoma de hipófise submetidos a tratamento cirúrgico endoscópico. A mucosa dos seios maxilares foi biopsiada no transoperatório; e no seio maxilar esquerdo foram aplicados 3 mL de mitomicina C tópica 0,5 mg/mL durante cinco minutos. No 21° dia pós-operatório, nova biópsia foi colhida nos seios maxilares. Nos seis pacientes submetidos à cirurgia transesfenoidal para exérese de tumor de hipófiise, realizou-se biópsia da mucosa normal do seio esfenoidal. As amostras foram analisadas por RT-qPCR para expressão de IL5, eotaxina, fator estimulador de colônia granulócito macrófago e fator transformador de crescimento beta-1. Resultados: observou-se, na mucosa doente, distribuição assimétrica para os valores das citocinas. Os valores de eotaxina diminuíram após o tratamento. No seio maxilar esquerdo, a expressão de IL5 foi maior no transoperatório (pré-aplicação de mitomicina C) em relação ao tecido normal e em relação ao 21º dia após a aplicação do medicamento. Conclusão: houve indicação da ação da mitomicina C na subexpressão da IL5. Verificou-se indicação do benefício da cirurgia e corticoide para eotaxina. As expressões das citocinas mostraram valores assimétricos e aumentados em relação ao tecido normal, exceto para o fator de crescimento beta-1.
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Barthel, Thomas [Verfasser], e Christoph [Akademischer Betreuer] Garlichs. "Einfluß von Statinen auf die Expression von TGF-ß1, VAP-1, Eotaxin3 und MIG als inflammatorische Trigger humaner hochgradig stenosierter und verkalkter Aortenklappen / Thomas Barthel. Betreuer: Christoph Garlichs". Erlangen : Universitätsbibliothek der Universität Erlangen-Nürnberg, 2013. http://d-nb.info/1034425714/34.
Testo completo
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Hollande, Clémence. "Rôle de dipeptidyl peptidase-4 dans la régulation du trafic leucocytaire au cours du carcinome hépatocellulaire". Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066446/document.
Testo completoAbstract (sommario):
La modification post-traductionnelle des chimiokines par la dipeptidyl peptidase-4 (DPP4 ou CD26) régule négativement le trafic des lymphocytes, et son inhibition améliore la migration des lymphocytes T et l'immunité anti-tumorale en préservant la forme fonctionnelle de CXCL10. En étendant ces résultats initiaux aux humains et à un modèle préclinique de carcinome hépatocellulaire, nous avons découvert un nouveau mécanisme par lequel l'inhibition de DPP4 améliore les réponses anti-tumorales par le recrutement des éosinophiles. Plus précisément, l'administration d'inhibiteurs de DPP4 (DPP4i) conduit à des concentrations tumorales plus élevées de CCL11 (ou eotaxine) et à une augmentation de la migration des éosinophiles exprimant CCR3 dans les tumeurs. Un meilleur contrôle de la croissance tumorale a été observé lors du traitement par DPP4i, un effet conservé chez les souris Rag2–/– mais abrogé uniquement lors de la déplétion des éosinophiles ou de l'inhibition de leur dégranulation. Nous avons également démontré que l'expression tumorale d’IL-33 était nécessaire et suffisante pour une réponse anti-tumorale médiée par les éosinophiles et que ce mécanisme contribuait à l'efficacité des inhibiteurs de points de contrôle immunitaires. Ces résultats révèlent un nouveau mécanisme par lequel le contrôle tumoral est médiée par IL-33 et les éosinophiles, mécanisme ici révélé lorsque les mécanismes endogènes de régulation immunitaire par DPP4 sont inhibésDipeptidyl peptidase-4 (DPP4 or CD26)–mediated post-translational modification of chemokines has been shown to negatively regulate lymphocyte trafficking, and its inhibition enhances T cell migration and tumor immunity by preserving functional CXCL10. In extending these initial findings to humans and pre-clinical hepatocellular carcinoma models, we discovered a new mechanism whereby DPP4 inhibition improves anti-tumor responses by eosinophil recruitment. Specifically, administration of DPP4 inhibitors (DPP4i) resulted in higher concentrations of CCL11 (or eotaxin) and increased CCR3-mediated eosinophil migration into mouse tumors. Enhanced tumor control was observed upon treatment with DPP4i, an effect strikingly preserved in Rag2–/– mice, and abrogated only upon depletion of eosinophils or inhibition of their degranulation. We further demonstrated that tumor expression of IL-33 was necessary and sufficient for eosinophil-mediated anti-tumor responses, and that this mechanism contributed to checkpoint inhibitor efficacy. These findings provide new insight into IL-33- and eosinophil-mediated tumor control, revealed when endogenous mechanisms of DPP4 immune regulation are inhibited
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Manns, Johanna [Verfasser]. "NNY-Eotaxin-CCL11 : Untersuchungen zur Auswirkung der N-terminalen Modifikation des Chemokins Eotaxin-CCL11 bezüglich seiner Rezeptorspezifität und seiner Stabilität / vorgelegt von Johanna Manns". 2006. http://d-nb.info/983425787/34.
Testo completo
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Stangenberg, Stefanie. "Rhinoviren stimulieren die Rantes- und Eotaxin-Produktion in nasalen Fibroblasten". 2006. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=016696067&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
Testo completo
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Pethe, Wolfram. "Zelluläre Quellen und Bedeutung von Eotaxin-2 bei der chronisch polypösen Sinusitis /". 2006. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=015026846&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
Testo completo
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"Intracellular signal transduction mechanisms regulating apoptosis and eotaxin release of human eosinophils". 2001. http://library.cuhk.edu.hk/record=b6073372.
Testo completoAbstract (sommario):
Zhang Jiping.Thesis (Ph.D.)--Chinese University of Hong Kong, 2001.
Includes bibliographical references (p. 157-179).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Mode of access: World Wide Web.
Abstracts in English and Chinese.
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LEE, HSI-MING, e 李錫銘. "Suppressive effects of formoterol and salmeterol on eotaxin-1 in bronchial epithelial cells". Thesis, 2009. http://ndltd.ncl.edu.tw/handle/uks939.
Testo completoAbstract (sommario):
碩士嘉南藥理科技大學
生物科技系曁研究所
97
Eotaxin-1 (CCL11), an eosinophil-specific C-C chemokine, is a potent chemoattractant for mobilization of eosinophils into airways after allergic stimulation. Eotaxin-1 could recruit eosinophils into inflammatory sites, and play a role in the pathogenesis of asthma. Formoterol and salmeterol are two inhaled long acting β2adrenoceptor agonists, widely used for the local treatment of asthma. However, little is known about their effects on the eotaxin-1 expression of bronchial epithelial cells. BEAS-2B cells were stimulated by adding IL-4 with or without 2h pretreatment of formoterol or salmeterol. The protein and mRNA expression of eotaxin-1 were measured by ELISA assay and real-time PCR, respectively. Effects of formoterol and salmeterol on nuclear and cytosolic p-STAT6 expression were evaluated by Western blot and immunofluorescence study. Formoterol and salmeterol (10-7~10-10 M) could significantly downregulate IL-4-induced eotaxin-1 expression in BEAS-2B cells. A specific β2 adrenoceptor antagonist (ICI 118,551) reversed their suppression of eotaxin-1 production. Forskolin, an cAMP activator, could also suppress the expression of eotaxin-1 by IL-4 in a dose dependent manner (10-7~10-10M). The Western and immunofluorescence studies demonstrated that formoterol 10-7M could suppress the nuclear expression of p-STAT6. Formoterol and salmeterol, two inhaled long-acting β2 agonists, downregulate IL-4- induced eotaxin-1 expression in BEAS-2B cells. The effect may be mediated via the β2 adrenoceptor, and cAMP. Formoterol downregulates p-STAT6 expression at higher concentration, and this further turn off the IL-4 signaling.
28
Essen, Eddy, e 張一旋. "Investigation on the mechanism of production of eotaxin in mice infected with Angiostrongylus cantonensis". Thesis, 2004. http://ndltd.ncl.edu.tw/handle/79923329774267268607.
Testo completoAbstract (sommario):
博士高雄醫學大學
醫學研究所博士班
92
There is evidence showing that eosinophils play an important role in non-permissive host reactions against Angiostrongylus cantonensis after infection. Eotaxin is the strongest mediator involved in eosinophil chemotaxis and chemokinesis, which selectively recruits eosinophils. In our study, all eotaxin concentrations weekly in the cerebrospinal fluid (CSF) of the infected mice were significantly higher than those in the serum and got the peak level at third weeks. The increases in eosinophils in CSF paralleled the kinetics of the change in eotaxin levels in the CSF of infected mice. Furthermore, in parallel with this CSF eosinophilia, infected mice showed gradual reductions in intracranial worm counts. Therefore, the high concentration of eotaxin in the CSF is a very important reason for the migration and recruitment of eosinophils. We used microchambers to demonstrate direct eosinophil chemotactic activity. The chemotactic response of eosinophils from the CSF weekly increase from week 1 to week 3. Adding a variety of antibodies into CSF from 21 days post-infection with A. cantonensis, the antibodies directly neutralized eotaxin, RANTES (regulated on activation, normal T-cells expressed and secreted), MIP (macrophage inflammatory protein) -1α or PAF (platelet-activating factor), respectively. Eosinophil migrated into the polycarbonate mambrane covering CSF with anti-eotaxin or anti-MIP-1α antibodies was significantly lower than that for antibody-free CSF (Student’s t tests: p < 0.01, p < 0.05). Furthermore, anti-RANTES and anti-PAF antibodies failed to inhibit the migration of eosinophils to the CSF. In conclusion, eotaxin release in the CSF of A.cantonensis-infected mice have eosinophil chemotactic activity in this in vitro assay. Th2 respones has been shown in mice infected with A. cantonensis. We wish to determine the kinetics of cytokine production and its possible role in expression of eotaxin in A. cantonensis infected mouse. Concentrations of IL (interleukin) -1β, IL-4, INF (interferon) -γ, IL-13 and TNF (tumor necrosis factor) -α in supernatants collected from different stimulated from APCs (antigen-presenting cells) and CD (cluster designation) 4+ T cells were assayed by ELISA (enzyme-linked immunosorbent assay). The conditioned medium collected form the medium preincubating APC and CD4+ T cells with IL-4 and then a second 85 μg/ml of A. cantonensis antigen stimulation expressing high level of IL-4. The conditioned medium were used to see the bioactivity of stimulating to the SVEC4-10 endothelial cells. Finally, only the conditioned medium with high level of IL-4 has the ability to stimulate SVEC4-10 endothelium cell expressing eotaxin. Although, the cytokine IL-1β, IL-13, IFN-γ and TNF-α also had the ability of stimulating cells to express eotaxin but in mouse infected with A. cantonensis seems only IL-4 may induce SVEC4-10 endothelial cells secreting eotaxin. We have demonstrated expressing of eotaxin for recruitment of eosinophils to CSF in mice infected with A. cantonensis and the necessary of IL-4 in expressing eotaxin in this study.
29
Spautz, Barbara Veronika. "Vergleichende Untersuchung der TNF-a-induzierten [TNF-alpha-induzierten] Eotaxin-CCL11-Expression durch primäre Fibroblasten". 2008. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=017646056&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
Testo completo
30
Li, Chao Yi, e 李昭儀. "Studies on the Relationship between the CC Chemokine Eotaxin-1 and the Progression of Osteoarthritis". Thesis, 2002. http://ndltd.ncl.edu.tw/handle/36317093020888327016.
Testo completoAbstract (sommario):
碩士台北醫學院
生物醫學技術研究所
90
We studied on the relationship between CC chemokine Eotaxin-1 and the progression of osteoarthritis. The concentrations of RANTES, MCP-1a and Eotaxin-1 in patients’ plasma with osteoarthritis (OA) are higher than those in normal plasma. Both the concentrations of RANTES and MCP-1a were decreased during injection of hyaluronan three times in patients with OA, while the concentration of Eotaxin-1 was significantly decreased at first time then it reversed. By reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbat assay (ELISA), we found that the expression of Eotaxin-1 mRNA in chondrocytes was induced by interlukin-1b (IL-1b) and tumor necrosis factor-a (TNF-a). Besides Eotaxin-1 was constitutively secreted after stimulation with IL-1b and TNF-a. Furthermore, Eotaxin-1 increased matrix metalloproteinase-3 (MMP-3) and MMP-13 messenger RNA (mRNA) expression but had no effect on TIMP-1 mRNA expression in chondrocytes. Eotaxin-1 induced both the expressions of CCR3 and CCR5 on cell surface, which analyzed by flow cytometry. Chondrocytes expressed CCR3 mRNA after stimulation with Eotaxin-1 while CCR5 mRNA was undetectable. To our knowledge, this is the first time to find human chondrocytes produce Eotaxin-1 in our study. We suggested that Eotaxin-1 might involve in cartilage degradation by inducing the expression of matrix metalloproteinases and CCR3.
31
Chen, Hong-Kong, e 陳杭港. "Studies of the molecular mechanisms of chemokine eotaxin-1 on the metalloproteinases expression in human chondrocyte". Thesis, 2004. http://ndltd.ncl.edu.tw/handle/16466985317383963137.
Testo completoAbstract (sommario):
碩士臺北醫學大學
生物醫學技術研究所
92
Osteoarthritis (OA) is characterized by loss of the functional integrity of articular cartilage due to an imbalance between catabolic and anabolic chondrocyte activity. Degradation of the collagenous extracellular matrix by metalloproteases (MMPs) plays an important role in the pathogenesis of osteoarthritis (OA). Our previous studies suggested that IL-1β、TNF-α could increase the expression of eotaxin-1 in human primary culture chondrocyte. Recently, we found that CCR3 receptor was a potential receptor for eotaxin-1 binding, and might be involved in MMP-3 expression. In this study, we investigated the molecular mechanism of eotaxin-1 on the MMP-3 expression and the possible role of eotaxin-1 in OA cartilage degradation. Similar to IL-1β,eotaxin-1 in significantly induced MMP-3 expression in both human chondrosarcoma cells SW-1353 and primary cultured chondrocyte by Western blot and RT-PCR. On the other hand, eotaxin-1 slightly induced the expression of tissue inhibitor of metallproterase-1(TIMP-1). To examine which signal pathway are involved in the MMP-3 expression by eotaxin-1, several kinase pathway are investigated the phosphorylation status. The results showed that eotaxin-1 significantly activated ERK, JUK and p38 MAPKs as well as Akt kinase in a time-dependent manner. In addition, ERK, p38 MAPKs, and PI3K inhibitor blocked the MMP-3 induction by Eotaxin-1. Treatment of NF-κB activation inhibitor could not affect the MMP-3 induction by eotaxin-1, suggesting that NF-κB pathway might not be involved in MMP-3 expression. These results provide evidence of the catabolic role of Eotaxin-1 in chondrocyte via up-regulation of MMP-3, and indicate that activation of ERK, p38 MAPK, and Akt are involved in the induction of MMP-3 by Eotaxin-1. Our results provide evidence of the catabolic role of Eotaxin-1 in chondrocyte via MMP-3 up-regulation. As well, understanding Eotaxin-1 induced signal pathway, therefore, it may give the conception of new therapeutic approaches for OA.
32
Liu, Keniji, e 劉賢一. "Expression level of Eotaxin, MCP-1, RANTES, CCR5, CCR3 and CCR2 of Taiwanese and Aboriginal Taiwanese". Thesis, 2002. http://ndltd.ncl.edu.tw/handle/75852654725438979912.
Testo completo
33
Jan, Ya-Yu, e 詹雅羽. "The Mechanisms of Eotaxin-2-induced toll-like receptor 4 expression in human coronary arterial endothelial cells". Thesis, 2014. http://ndltd.ncl.edu.tw/handle/34k6zv.
Testo completoAbstract (sommario):
碩士臺北醫學大學
醫學檢驗暨生物技術學系所
102
Objective: Eotaxin-2 interacts with toll-like receptor 4 (TLR4) and induces inflammatory responses in human coronary arterial endothelial cells (HCAECs), which plays an important role in atherogenesis. The objective of this study was to investigate the mechanisms involving eotaxin-2-induced TLR4 expression in HCAECs. Methods and results: Stimulation via eotaxin-2 significantly increased TLR4 mRNA level in HCAECs by real time polymerase chain reaction (RT-PCR). In addition, on eotaxin-2 treatment also increased TLR4 protein expression. An actinomycin D chase experiment showed that eotaxin-2 increased the stability and half life of TLR4 mRNA. Immunocytofluoresence data showed that after treated HCAECs with eotaxin-2, human antigen R (HuR) translocated from nucleus to cytoplasm. Eotaxin-2 induced 3’UTR of TLR4 mRNA-containing luciferase plasmid expression in HCAECs. These results showed that the HuR modultes 3’untranslated region (3’UTR)-mediated gene expression. On the other hand, RT-PCR demonstrated that eotaxin-2-induced TLR4 mRNA expression was reduced by SB203580 (a p38 MAPK inhibitor) or PD98059 (an ERK1/2 inhibitor) , but not by SP600125 (an SAPK/JNK inhibitor). However, eotaxin-2-induced TLR4 protein expression was reduced by SB203580 or SP600125, but not by PD98059. Conclusion: Activation of HuR and the mitogen-activated protein kinase(MAPK)-signaling pathways contribute to eotaxin-2-induce TLR4 mRNA and protein expression in HCAECs.
34
Chao, Pin-Zhir, e 趙品植. "Levels of RANTES, Eotaxin in the patients with chronic rhinosinusitis and its correlation with severity of the disease". Thesis, 2004. http://ndltd.ncl.edu.tw/handle/nc9gu9.
Testo completoAbstract (sommario):
碩士臺北醫學大學
醫學研究所
93
Chronic rhinosinusitis and nasal polyps mainly develop in the ethmoid sinus, maxillary sinus and middle turbinate area, often in relation to inflammatory and allergic conditions. Their exact etiology and pathogenesis are still under debate. Histologically, inflammatory cell infiltrations of nasal mucosa predominated by eosinophils are typical for such disease, and may be due to the chemotactic activity of chemokines specific for eosinophils. This findings suggest that nasal polyp is an inflammatory growth that is controlled by the local environment and the immunologic defense mechanism of the host. The CC-chemokine Eotaxin and RANTES (regulated on activation normal T cell expressed and secreted) have been postulated to be involved in the recruitment of eosinophils toward inflamed tissues. To explore their possible roles in chronic rhinosinusitis, we examined the concentraion of Eotaxin and RANTES protein in the serum of patients and correlated these results to the severity of disease graded by sinus CT imaging. Serum samples were obtained from 20 of patients undergoing endoscopic sinus surgery, and blood samples of 20 normal control subjects were also drawn. Enzyme-linked immunosorbent assay(ELISA) for Eotaxin and RANTES protein of serum was performed, and the relationship between these results and the Lund-MacKay rhinosinusitis scoring system and the percentage of peripheral eosinophil were investigated. In comparison to normal control group, we found significant elevation of Eotaxin and RANTES protein in the serum of experimental group(p<0.05). The levels of serum Eotaxin and RANTES in patients were correlated with the severity of the disease; with Eotaxin showed a more statistical significance. Besides, RANTES and Eotaxin levels were correlated with the percentage of peripheral eosinophil(p<0.05). These data suggest that, in patients of chronic rhinosinusitis with nasal polyp, disease severity correlates mainly with Eotaxin, and that RANTES may play a less important role in the mobilization of eosinophils from the blood into inflamed tissues. Further larger experiment was anticipated to validate this correlation.
35
Chu, Yu-Te, e 朱育德. "The changes of serum eotaxin, eosinophil cationic protein, and eosinophil count while treating pediatric asthmatic patients with steroids". Thesis, 2006. http://ndltd.ncl.edu.tw/handle/93255409129338112410.
Testo completoAbstract (sommario):
碩士高雄醫學大學
醫學研究所碩士班
94
Background: Increased serum level of eotaxin is related to asthma severity in adult study. There is little data about pediatric asthma patients with regards to the effects of oral and inhaled corticosteroids on serum eotaxin, eosinophil cationic protein (ECP) concentrations and eosinophil counts. Methods: We investigated prospectively the changes of serum level of eotaxin, eosinophil counts, and ECP after oral steroid for one week and then inhaled corticosteroids with a long–acting β2 agonist (Seretide) treatment for 2 months in the pediatric population. The data of serum eotaxin, ECP, and blood eosinophil count were collected. The peak expiratory flow (PEF) was used as outcome index and correlation study with previous inflammation markers was performed. Results: The serum level of eotaxin persisted after one-week oral prednisolone treatment, but decreased after subsequent inhaled corticosteroids with a long–acting β2 agonist treatment (85.7±36.8 vs. 64.7±22.6 pg/ml, p<0.001). The eosinophil count and ECP declined soon after oral steroid treatment, but rebounded to the same level during inhaled treatment. The decline of ECP is positively correlated with the decline of eosinophil count while oral steroid treatment (r2 =0.28, p=0.016). There was no correlation between changes in eotaxin and PEF. Conclusion: There is discrepancy of serum concentration of eotaxin, ECP and blood eosinophil count during the treatment of oral steroid and inhaled corticosteroids. Our data suggested that the serum eotaxin level, not eosinophil count or ECP, declined during inhaled corticosteroids with a long–acting β2 agonist treatment and might serve as a surrogate marker of Th2 residual activity in treating pediatric asthma. The concentration of eotaxin could not predict the changes of PEF.
36
潘潔宜. "Studies on the possible signaling pathways of eotaxin-1 induced matrix metalloproteinase-3 (MMP-3) expression in human chondrocyte". Thesis, 2003. http://ndltd.ncl.edu.tw/handle/78225054534827588023.
Testo completo
37
Karsten, Claudia. "Untersuchungen zur Potenz von respiratorischen Zellen im Hinblick auf die Expression von Eotaxin und Exotaxin-3 bei labortechnischer Simulation einer proinflammatorischen Entzündung". 2004. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=014189918&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
Testo completo
38
Knott, Michelle Louise. "Host-parasite interactions in primary and secondary infections with Nippostrongylus brasiliensis and Heligmosomoides bakeri". Thesis, 2010. http://hdl.handle.net/2440/67240.
Testo completoAbstract (sommario):
Parasitic helminth infections are a significant problem worldwide. Some helminth species are becoming resistant to current therapies and new forms of treatment and/or vaccines are required. Nippostrongylus brasiliensis is a tissue-invasive parasitic helminth that infects rodents, and the lifecycle of this parasite is similar to that of the human hookworms. The aims of this study were to investigate primary and secondary immune responses to N. brasiliensis, focusing on the pre-lung phase of infection. The roles of cytokines, chemokines, signalling pathways and leukocytes such as eosinophils were investigated in the skin, lungs and small intestine. The roles of eosinophils were also investigated in primary infections with the intestinal nematode Heligmosomoides bakeri. Interleukin (IL)-5 is important for eosinophil development and maturation and for protection during some helminth infections. Over-expression of IL-5 provides potent protection in primary infections with N. brasiliensis in the pre-lung phase of infections. Although mice deficient in IL-5 or eosinophils might therefore be predicted to be more susceptible to N. brasiliensis, IL-5-deficient (IL-5⁻/⁻) and eosinophil-deficient (ΔdblGATA) mice showed similar infection patterns as wildtype (WT) mice during primary N. brasiliensis infections. Intestinal worm and/or egg numbers however were elevated in mice with defective eosinophilopoiesis compared with WT animals. In secondary infections, despite skin inflammatory responses (4 hours p.i.) being similar in WT, IL-5⁻/⁻ and ΔdblGATA animals, at day 2 p.i., lung larval burdens in the two latter hosts were significantly higher than in the resistant WT controls. However, parasites were expelled from intestines of all mice by day 7 of secondary infections. These data suggest that in the pre-gut phase of secondary infection, IL-5 and eosinophils play an important role in resistance to N. brasiliensis. Despite this, eosinophils do not appear to be essential for protection mediated within the gut during secondary infections, even though IL-5 and eosinophils do appear to confer some protection in the gut during primary infections. Complement is required for the recruitment of eosinophils into the skin in the first 150 minutes of primary infection with N. brasiliensis (Giacomin et al., 2008a), however other chemotactic factors appear to be involved after this time. Although eotaxin is chemotactic for eosinophils in some tissues, the importance of eotaxin and signalling pathways involved in expression of this chemokine has not been previously characterized in N. brasiliensis infections. Signal transducer and activator of
transcription (STAT)6 is a key transcription factor in the IL-4/IL-13 signalling pathway and these cytokines can induce expression of eotaxin in some tissues. Expulsion of N. brasiliensis adult worms during primary infections is profoundly impaired in STAT6- deficient (STAT6⁻/⁻) mice. IL-5 Tg mice are highly resistant to primary infections with N. brasiliensis and in the current study, it was shown that ablation of eotaxin-1 or STAT6 in IL-5 Tg mice did not impair the strong innate resistance typically seen in the pre-lung phase of N. brasiliensis infections. While recruitment of eosinophils to the skin (4 hours p.i.) was reduced in these mice compared with IL-5 transgenic (Tg) mice, protective capacity was preserved in both primary and secondary infections. Further, eotaxin-1⁻/⁻ single mutant mice were strongly resistant to secondary N. brasiliensis infections, with few larvae migrating to the lungs on day 2 p.i. In contrast, STAT6⁻/⁻, IL-13⁻/⁻, IL-4Rα⁻/⁻ and IL-13⁻/⁻/IL-4Rα⁻/⁻-double deficient mice had significantly higher secondary lung larval burdens than WT mice and parasite egg production was prolonged in all of these strains. These data suggest a role for this signalling pathway in protection during the early stages of secondary infections with this parasite. In both primary and
secondary infections, eosinophils were recruited to the skin in all gene knock out strains in comparable numbers to those seen in WT mice, and this suggests that alternative eosinophil recruitment pathways may compensate for the absence of these factors. Adding to the extensive work on the intestinal phase of N. brasiliensis, this work clearly indicates for the first time that early pre-lung events are crucial in determining the outcome of infection, and should be the focus of future studies with N. brasiliensis. In contrast, when STAT6- and eotaxin-1-deficient mice were infected with another intestinal nematode, H. bakeri, the mutant strains were as susceptible as WT mice, with parasite eggs present in similar numbers on all days examined. Resistance mechanisms that operate in the intestine during N. brasiliensis infections do not therefore appear to extend to a parasite that can infect naïve hosts for many months. The FVB/N mouse strain was introduced into this study whilst exploring the potential roles of eosinophils in the intestinal phase of N. brasiliensis infections. The impact of intestine-specific expression of transgenes encoding IL-5 and eotaxin-1 were examined and although both lines of Tg mice were highly resistant to N. brasiliensis, naïve WT FVB/N mice also showed very potent innate resistance. Very few worms were observed in the small intestine of WT FVB/N animals on day 7 p.i., whereas skin larval and leukocyte numbers (4 hours p.i.) and lung larval burdens (day 2 p.i.) were similar in WT FVB/N and WT CBA/Ca mice. Interestingly, lung larvae recovered from WT FVB/N animals were significantly smaller in size (days 1-2 p.i.) and less motile than lung larvae recovered from WT CBA/Ca mice. Further, there were significantly fewer eggs (day 6 p.i.) and worms (day 7 p.i.) in the former. However, WT FVB/N mice were no more resistant to infections with H. bakeri than WT CBA/Ca mice, with parasite eggs detected in comparable numbers until day 116 p.i. Resistance mechanisms operating against N. brasiliensis in WT FVB/N mice would not therefore appear to extend to H. bakeri infections. Eosinophils can provide potent protection in some helminth infections and this study builds on our previous work and that of other groups. We have now shown that early pre-lung events may be critical in determining host resistance against N. brasiliensis. In secondary N. brasiliensis infections, cytokine signalling pathways that protect against adult worms in the late intestinal phase of infection also play a role in resistance during the early pre-lung phase, when the parasite is still at the larval stage. Eosinophils are also of importance for protection against this parasite, and future studies should focus on the early events to further characterize resistance mechanisms. This information may prove useful for the development of successful vaccines against hookworms and other nematodes.Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2010
39
Mwanthi, Muithi. "PAK1's regulation of eosinophil migration and implications for asthmatic inflammation". Thesis, 2013. http://hdl.handle.net/1805/3786.
Testo completoAbstract (sommario):
Indiana University-Purdue University Indianapolis (IUPUI)More than 300 million people world-wide suffer from breathlessness, wheezing, chest tightness, and coughing characteristic of chronic bronchial asthma, the global incidence of which is on the rise. Allergen-sensitization and challenge elicits pulmonary expression of chemoattractants that promote a chronic eosinophil-rich infiltrate. Eosinophils are increasingly recognized as important myeloid effectors in chronic inflammation characteristic of asthma, although few eosinophil molecular signaling pathways have successfully been targeted in asthma therapy. p21 activated kinases (PAKs), members of the Ste-20 family of serine/threonine kinases, act as molecular switches in cytoskeletal-dependent processes involved in cellular motility. We hypothesized that PAK1 modulated eosinophil infiltration in an allergic airway disease (AAD) murine model. In this model, Pak1 deficient mice developed reduced inflammatory AAD responses in vivo with notable decreases in eosinophil infiltration in the lungs and broncho-alveolar lavage fluids (BALF). To test the importance of PAK1 in hematopoietic cells in AAD we used complementary bone marrow transplant experiments that demonstrated decreased eosinophil inflammation in hosts transplanted with Pak1 deficient bone marrow. In in vitro studies, we show that eotaxin-signaling through PAK1 facilitated eotaxin-mediated eosinophil migration. Ablating PAK1 expression by genetic deletion in hematopoietic progenitors or siRNA treatment in derived human eosinophils impaired eotaxin-mediated eosinophil migration, while ectopic PAK1 expression promoted this migration. Together these data suggest a key role for PAK1 in the development of atopic eosinophil inflammation and eotaxin-mediated eosinophil migration.