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Kerscher, Berhard Gerhard Richard. "Characterisation of the C-type lectin receptor Clecsf8". Thesis, University of Aberdeen, 2016. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=230779.
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C-type lectin-like receptors (CTLRs) play critical roles in immunity and homeostasis by recognising a variety of microbial or endogenous ligands. Clecsf8 is a member of the Dectin-2 family of CTLRs. Clecsf8 shares important similarities with its relatives Mincle and Dectin-2, such as the lack of an integral signalling motif and a single, calcium dependent ligand binding domain. They were shown to associate with the FcRγ adaptor, which is essential for receptor surface expression and downstream signalling. Recent publications revealed an important role for Clecsf8 in anti-mycobacterial immunity. It was reported to recognise the mycobacterial cord factor (TDM), similar to the related CTLR Mincle, as well as a possible role in candidiasis. In this study, we characterised the underlying mechanism of Clecsf8 expression in a context of mycobacterial disease. The generation of novel anti-Clecsf8 monoclonal antibodies allowed us to characterise the expression of Clecsf8 in detail in homeostasis and inflammation in murine models in vivo and culture systems in vitro. We found Clecsf8 to be predominantly expressed on monocytes/macrophages and neutrophils within e. g. the peritoneal cavity, blood and bone marrow. Notably, Clecsf8 was expressed only weakly in the lung, but strongly upregulated in a pulmonary mycobacterial infection model. In vitro, Clecsf8 expression on elicited macrophages was strongly induced upon treatment with microbial stimuli in a Myd88- and Mincle dependent manner. Interestingly, surface expression of Clecsf8 in a murine fibroblast cell line was greatly enhanced by co-transfection of Mincle, but not another related CTLR, Dectin-2. Notably, we confirmed mycobacteria as a ligand of CLECSF8, but found no role for the receptor in Candida immunity. In conclusion, Clecsf8 is a myeloid expressed, mycobacterial receptor, showing significant interdependence with Mincle and is regulated through the Myd88 pathway.
2
Nassanian, Hoorig. "The biology of the C-Type lectin receptor DC-SIGN". Diss., Restricted to subscribing institutions, 2008. http://proquest.umi.com/pqdweb?did=1627802281&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Clark, Alexandra Elsie. "Characterisation of the C-type lectin-like receptor 1 (CLEC-1)". Thesis, University of Aberdeen, 2013. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=210080.
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Marshall, Andrew. "The characterisation of a novel C-type lectin-like receptor MICL". Thesis, University of Oxford, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.409114.
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Huysamen, Cristal. "The characterization of a novel C-type lectin-like receptor, CLEC9A". Doctoral thesis, University of Cape Town, 2008. http://hdl.handle.net/11427/3060.
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Murase, Takatoshi. "Identification of soluble forms of lectin-like oxidized LDL receptor-1". Kyoto University, 2004. http://hdl.handle.net/2433/148276.
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Rumjantseva, Viktoria. "Dual roles for hepatic lectin receptors in the clearence of chilled platelets /". Göteborg : Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine, The Sahlgrenska Academy, University of Gothenburg, Department of Translational Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Göteborg and Boston, 2009. http://hdl.handle.net/2077/21173.
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8
Rogers, Sarah Louise. "Characterisation of C-type lectin-like receptor genes in the chicken MHC". Thesis, University of Bristol, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271871.
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Souto, Maior Mourão Sá D. "Characterisation of the C-type lectin receptor CLEC-2 : expression, ligands and functions". Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1302407/.
Texto completo da fonteResumo:
Myeloid cells express a plethora of C-type lectin receptors (CLR) that can regulate inflammatory responses. Dectin-1 belongs to a sub-family of CLRs that possesses an extracellular C-type lectin domain (CTLD) and a single YxxL intracellular motif (hemITAM) that allows signalling via Syk kinase and induction of downstream functions. Based on consensus sequences for the CTLD and hemITAM, we identified CLEC-2 as a dectin-1-like receptor. CLEC-2 was previously characterised as a Syk-coupled platelet receptor able to induce platelet aggregation when targeted by the snake venom rhodocytin and by cells expressing the endogenous protein podoplanin. I generated monoclonal antibodies against mouse CLEC-2 and found that CLEC-2 is also expressed on lymphoid and myeloid cells, including dendritic cells (DC). Notably, treatment with LPS increases CLEC-2 expression by myeloid cells and synergises with CLEC-2 signaling to induce increased secretion of IL-10 but not IL-12. This increased IL-10 production is also observed in the serum of mice administered with anti-CLEC-2 mAb and LPS, and is dependent on the presence of macrophages and DCs. Furthermore, I generated a CLEC-2 conditional KO mouse line that will provide a tool to study CLEC-2 function in myeloid cells in vivo. Collectively, these data indicate that CLEC-2 expression is not restricted to platelets and that it plays a role on the vascular development and modulation of TLR responses.
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Tessmer, Marlowe S. "Biological functions and molecular associations of the killer cell lectin-like receptor G1". View abstract/electronic edition; access limited to Brown University users, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3318364.
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Mthembu, Nontobeko F. "Investigating the role of the Dendritic Cell Immunoactivating Receptor in the Immune Response during Pneumocystis murina". Master's thesis, Faculty of Health Sciences, 2020. http://hdl.handle.net/11427/32291.
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Pneumocystis jirovecii causes fungal pneumonia in immunocompromised patients and can be fatal if left untreated. The global mortality rate is estimated to be over 200 000 in AIDS patients. In non-AIDS patients there is an estimated mortality rate of 50 000 cases. This rate is increasing in developed countries, attributed to an increase in disorders which require immunotherapy. These include hematologic malignancies, organ transplant, inflammatory disorders and pre-existing lung disease. Immediate immunity is initiated by receptors that recognize pathogen associated molecular patterns on the surface of pathogenic fungi. Specifically, C-type lectin receptors (CLRs) have been shown to be the principal initiators of innate immune response during fungal infection. Limited studies have focused on the role of CLRs in Pneumocystis infection. Dectin1and Mincle have been shown to recognise Pneumocystis surface antigens with Dectin-1 recognizing β-glucans on the Pneumocystis cell wall leading to an effective immune response. However, the role of a newly described CLR, the Dendritic Cell Immunoactivating Receptor (DCAR) remains undefined. For this reason, we investigated the potential role of this receptor in a mouse model of Pneumocystis murina infection. Wild type and DCAR-deficient C57BL/6 mice were infected with P. murina organisms via intratracheal instillation. Fungal burden was measured in the lung using quantitative Polymerase Chain Reaction. DCAR-deficient mice had a significantly reduced burden compared to wild type mice at Day 7 and 14 post-infection. To identify the immune components involved in pathogen clearance in these mice we measured cellular recruitment and cytokine production at both early (48 hours) and late (7, 14 and 21 days) time points. Flow cytometry analysis showed an increase in alveolar macrophage, dendritic cells, inflammatory monocytes, eosinophils and T cell recruitment to the lung. While ELISA showed increased levels of IL-1β and IFN-γ at 48 hours, and later on in infection IL-1β and IL-12p40 levels were also elevated. Histology analysis determined the localization of the recruited cells, and v interestingly showed an increase in mucus production at day 21 in DCARdeficient mice. In conclusion, we have identified DCAR deficiency as a potential driver of protective immunity in mice during P. murina infection. This may be associated with increased levels of IL-1β in DCAR-deficient mice. Furthermore, DCAR may also be important in adaptive inflammatory response regulation, as DCAR-deficient mice have increased cellular recruitment and mucus production later in infection. The mechanism by which the deletion of this receptor affords these mice the ability to efficiently clear P. murina remains to be determined.
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Salvage-Jones, Judith. "The Macrophage Inducible C-type Lectin (Mincle) is a Receptor for the Yeast, Candida Albicans". Thesis, Griffith University, 2017. http://hdl.handle.net/10072/367510.
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The Macrophage-Inducible C-type Lectin (Mincle) belongs to the family of C-type lectin receptors some of which have been well characterised. We investigated a role for Mincle in response to systemic candidiasis both in vivo and ex vivo.
Our results show that while Mincle recognises C. albicans it is not phagocytic or candicidal. It does however, recognise this yeast as measured by reduced TNF-α production in Mincle deficient bone marrow-derived macrophages. Furthermore, there was a significant reduction in the cytokines KC, IL-1β, IL-10, IL-13, GCS-F, MIP-1β and RANTES in these cells.
By using a mouse model of systemic infection, we were able to investigate levels of yeast fungal burden and tissue damage inMincle-/- and isogenic control mice. Mincle deficient mice were more susceptible to C. albicans infection, demonstrated by increased fungal burden and increased tissue damage in the kidney and brain of our knock-out mice, confirming a role for Mincle in control of C. albicans infection.
Mincle shares some features in common with the β-glucan receptor (Dectin-1) and its close relative Dectin-2. Dectin-1 and Dectin-2 have both been shown to recognise the yeast Candida albicans. We therefore, went on to look at the RNA and protein expression profiles of these three C-type lectins and found Mincle was consistently upregulated in response to Candida in the brain, kidney, lung and spleen. Dectin-1 showed delayed induction and Dectin-2 was significantly up-regulated in all tissues in the absence of Mincle.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Natural Sciences
Science, Environment, Engineering and Technology
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Mitsuoka, Hirokazu. "Interleukin 18 stimulates release of soluble lectin-like oxidized LDL receptor-1(sLOX-1)". Kyoto University, 2008. http://hdl.handle.net/2433/124235.
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Surovy, André Martin. "Toll like Receptor 2 is highly expressed in lesions of Acne Inversa and colocalizes with C-type Lectin Receptor expression /". Bern : [s.n.], 2007. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Leoratti, Fabiana Maria de Souza. "Influência de variantes de receptores de reconhecimento padrão na suscetibilidade à malária". Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5160/tde-19112008-173242/.
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Malária é uma das principais causas de doença e morte no mundo, principalmente de crianças. É considerada a força de seleção evolucionária mais forte que se conhece na história recente do genoma humano. Além dos fatores ambientais e do próprio parasito, fatores genéticos do hospedeiro têm um papel fundamental tanto na suscetibilidade como na evolução clínica da infecção. O sistema imune inato reconhece os plasmódios através de um número limitado de receptores de reconhecimento padrão (PRRs) e inicia vários mecanismos de defesa que resultam no desenvolvimento de inflamação e resistência do hospedeiro à infecção. Mas, a eliminação completa do parasito requer respostas imunes adaptativas que são amplificadas pela ativação do sistema imune inato. As manifestações clínicas de malária são dependentes dos níveis de citocinas próinflamatórias circulantes produzidas, as quais em níveis altos contribuem para a imunopatologia da doença. O balanço entre respostas pró e antiinflamatórias dirigidas contra o parasito é considerado crítico para a proteção clínica, assim a resposta imune inata pode contribuir tanto para proteção da malária como para modular a resposta imune adaptativa. Neste estudo, nós investigamos polimorfismos de um único nucleotídeo (SNP) dos genes de três PRRs: TLR, MBL e CR1 de indivíduos infectados por Plasmodium e residentes em áreas endêmicas de malária no Brasil. Os SNPs TLR1 (I602S), TLR4 (D229G), TLR6 (S249P), TLR9 (T-1237C/ -1486C), MBL [exon 1 nos códons 52, 54, e 57 (MBL2*A ou D, A ou B e A ou C, respectivamente); na região do promotor na posição -221 (*X ou *Y); e na posição +4 da região não traduzida (*P ou *Q)] e CR-1(C5507G) foram determinados por PCR-RFLP. Nós observamos associações entre os polimorfismos TLR1 I602S, TLR6 S249P e da região não traduzida +4 (*Q) e manifestações clínicas de malária e entre os polimorfismos TLR9 T-1486C, TLR T-1237C, MBL*D (códon 52) e do diplótipo de produção insuficiente de MBL (XA+O/O) e parasitemias mais altas. Nenhuma associação foi observada entre o polimorfismo CR-1 C5507G e manifestações clínicas de malária ou com parasitemia. Ao analisarmos juntos os polimorfismos de MBL e TLR, observamos que indivíduos com diplótipo de produção suficiente de MBL (YA/YA+YA/XA+YA/O+XA/XA) TLR1 I602S tinham menos manifestações clínicas de malária e indivíduos com diplótipo de produção suficiente de MBL e não carreadores do alelo TLR9 -1486C tinham parasitemias mais baixas do que os indivíduos com diplótipo de produção insuficiente de MBL e carreadores dos alelos variantes de TLR1 I602S e TLR9 -1486C, respectivamente. Juntos, nossos dados indicam que polimorfismos do promotor de TLR-9 e os diplótipos de produção insuficiente de MBL (XA+O/O) devem de algum modo controlar o nível de parasitemia por plasmódios enquanto a deficiência de TLR1 parece predispor para a presença de manifestações clínicas de malária. Também, podemos sugerir que existe uma cooperação entre TLR1, TLR9 e MBL na ativação da resposta imune inata na malária. Estes achados genéticos devem contribuir para o entendimento da patogênese da malária e levantar uma questão potencialmente interessante que é digna de investigações posteriores em outras populações a fim de validar a contribuição genética destes loci na patogênese da maláriaMalaria is one of the major causes of disease and death worldwide, mainly of children. It is also the strongest known force for evolutionary selection in the recent history of the human genome. Besides environmental and parasite factors, host genetic factors play a major role in determining both susceptibility to malaria and the course of infection. Innate immune mechanisms directed against Plasmodium parasites both contribute to protection from malaria and modulate adaptive immune responses. The innate immune system recognizes Plasmodium via a limited number of pattern-recognition receptors (PRRs) and initiates a broad spectrum of defense mechanisms that result in the development of inflammation and host resistance to infection. But, the complete control of the infection requires adaptive immune responses; and the innate immune system is also very efficient in instructing the cellular mediators of adaptive immunity to lead a powerful additional strike force against the parasite. Clinical malaria is characterized by high levels of circulating proinflammatory cytokines, which are thought to contribute to the immunopathology of the disease. The balance between pro- and anti-inflammatory responses toward the parasite is considered critical for clinical protection. The innate immune system initiates and thus sets the threshold of immune responses. In this study, we investigated single nucleotide polymorphisms (SNP) in the genes of three PRRs: TLR, MBL and CR1 in Plasmodium-infected individuals living in endemic areas of Brazil. The SNPs TLR1 (I602S), TLR4 (D229G), TLR6 (S249P), TLR9 (T-1237C/ -1486C), MBL [in the coding sequence of exon 1 at codons 52, 54, and 57 (MBL2*A or D, A or B, and A or C, respectively); in the promoter region at position -221 (*X or *Y); and in the untranslated sequence at position +4 (*P or *Q)] and CR-1(C5507G) were determined by PCR-RFLP. We observed associations of the TLR1 I602S, TLR6 S249P and untranslated sequence at position +4 MBL (*Q) variants with clinical manifestations of malaria and of the TLR9 T-1486C, TLR9 T-1237C, MBL2*D and MBL-insufficient diplotype (XA+O/O) with higher parasitemias. No association was observed to the CR-1 C5507G ) and clinical manifestations of malaria or parasitemia. Also, we observed that individuals with MBLsufficient haplotype (YA/YA+YA/XA+YA/O+XA/XA) and not bearing the allele TLR1 I602S had less clinical manifestations of malaria and individuals with MBL-sufficient haplotype and not bearing TLR9 -1486C had lower parasitemias when compared to individuals with MBL-insufficient diplotype and bearing the variant alleles TLR1 I602S and TLR9 -1486C, respectively. Altogether, our data indicate that TLR-9 promoter and MBL-insufficient haplotype (XA+O/O) polymorphisms to some extent may control the level of Plasmodium parasitemia while TLR1 deficiency seems to predispose to mild malaria. Also, they could suggest cooperation among TLR1, TLR9 and MBL in the immune response against malaria. These genetic findings may contribute to the understanding of the pathogenesis of malaria and raise a potentially interesting issue that is worthy of further investigation in other population in order to validate the genetics contribution of these loci to the pathogenesis of malaria
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Shiu, Wing-ming Sammy, e 邵永明. "Role of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) in diabetes mellitus". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B50534075.
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Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) is a recently identified scavenger receptor expressed in endothelial cells and mediates the uptake of oxidized LDL (oxLDL). LOX-1 expression is increased in atherosclerotic lesions in animals and humans. Recent evidence has suggested that LOX-1 is involved in the development and progression of atherosclerosis. In addition to endothelial cells, it has also been reported that LOX-1 is also expressed by other cell types like macrophages. It is a multi-ligand class E scavenger receptor and cellular expression of LOX-1 can be induced by many of its ligands. The concentration of some of these ligands like oxLDL and advanced glycation end products (AGEs) are increased in the diabetic milieu. My hypothesis is that LOX-1 expression is increased in diabetes mellitus and LOX-1 activation may play a role in the development of micro- and/or macrovascular complications of diabetes. The objective of this thesis is to elucidate the role of LOX-1 in type 2 diabetes mellitus and its complications. The effect of modified LDL and AGEs on LOX-1 expression and the cellular response upon LOX-1 activation was investigated.
In vitro studies have shown that both AGEs and oxLDL can activate and increase cellular expression of LOX-1 and the soluble form of LOX-1 (sLOX-1) in cultured endothelial cells. In addition, LDL modified by glycoxidation, is also a ligand of LOX-1 and glycoxidized LDL is even more potent than oxLDL in inducing LOX-1 expression. In patients with type 2 diabetes, serum level of sLOX-1 was significantly higher than non-diabetic normal control, indicating that LOX-1 expression was increased in diabetes. Serum levels of AGEs and glycoxidized LDL were important determinants of serum sLOX-1 level, and lowering serum AGEs led to a beneficial reduction in serum sLOX-1 concentration. Hence, AGEs was clearly an important ligand of LOX-1 in diabetes mellitus, and experiments were performed to further elucidate the underlying signaling pathway involved in the up-regulation of LOX-1 by AGEs. This was mediated by ligation of AGEs to the receptor for advanced glycation end products (RAGE) and activation of phosphoinositide 3-kinase. Mammalian target of rapamycin was a found to be a key downstream intermediary in AGEs-inducible LOX-1 expression in endothelial cells. I further demonstrated that LOX-1 was also expressed in human renal mesangial cells, and expression was at a low level at basal state but inducible by its ligands. Up-regulation of LOX-1 expression in activated mesangial cells resulted in increased oxidative stress, as well as increased production of proinflammatory cytokines, chemokines and growth factors. These experimental findings would suggest that LOX-1 might potentially be involved in renal inflammation and diabetic nephropathy.
The above results collectively suggest that diabetes is associated with increased LOX-1 activation, and LOX-1 may play a role in the development of diabetic complications. Hence, LOX-1 might represent a suitable target for the future development of new strategies for treating and preventing diabetic vascular complications.published_or_final_version
Medicine
Doctoral
Doctor of Philosophy
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Hoshikawa, Hajime. "High affinity binding of oxidized LDL to mouse lectin-like oxidized LDL receptor (LOX-1)". Kyoto University, 1999. http://hdl.handle.net/2433/182282.
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Asamaphan, Patawee. "Exploring the structure and function of MelLec, a C-type lectin-like receptor that recognises DHN melanin". Thesis, University of Aberdeen, 2018. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=239859.
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Peric, Alexander A. [Verfasser]. "Die Rolle des lectin-like oxidized lipoprotein receptor-1 in der postviralen Pneumokokkenpneumonie / Alexander A. Peric". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2017. http://d-nb.info/1133492630/34.
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Hanske, Jonas [Verfasser]. "Investigation of the Structural Basis of Ligand Recognition of the C-Type Lectin Receptor Langerin / Jonas Hanske". Berlin : Freie Universität Berlin, 2016. http://d-nb.info/1121587895/34.
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Hanc, P. "Structural and biochemical characterisation of the C-type lectin receptor DNGR 1 and its binding to F-actin". Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1472936/.
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DNGR-1 is a C-type lectin receptor that has been implicated in the regulation of endocytic trafficking and cross-presentation of dead cell-associated antigens. Dendritic cells deficient in DNGR-1 are impaired in priming effector T-cell responses against cytopathic viruses and other dead cell-associated antigens. The ligand for DNGR-1 is the polymerized form of actin (F-actin) revealed in dead cells upon loss of membrane integrity. In this study we set out to determine biophysical, biochemical, and structural properties of DNGR-1 and its interaction with F-actin. First, we describe a conformational change that occurs in the neck region of the receptor in a pH- and ionic strength-dependent manner. Notably, the conformational change happens between conditions corresponding to the extracellular environment and the environment present in the vesicles of the endosomal pathway respectively, suggesting a possible role in the spatial regulation of the DNGR-1 function. Second, in collaboration with Keichii Namba and Takashi Fujii (RIKEN Quantitative Biology Center, Osaka, Japan) we used electron cryomicroscopy to solve the structure of DNGR-1 bound to F-actin at 7.7 Å resolution. Interestingly, DNGR-1 binds into the groove between actin protofilaments, making contacts with three actin subunits that are helically arranged in the F-actin structure. We identify the residues directly involved in the interaction, confirm their contribution to the binding and demonstrate the importance of avidity of the multivalent interaction between DNGR-1 and F-actin. Additionally, in collaboration with David Sancho and Salvador Iborra (Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain) we formally demonstrate that ligand recognition is prerequisite for the biological function of DNGR-1 in dendritic cells. Third, by using heterodimeric DNGR-1 proteins in which one half of the dimer is incapable of binding to ligand, we demonstrate that DNGR-1 can bind with both ligand binding domains to a single actin filament, suggesting an exceptional flexibility of the neck region, and demonstrating an absence of rigid dimerization interface between the ligand-binding domains. In summary, we provide a comprehensive description of the structural and biophysical properties of DNGR-1, offering novel insights into its function and shedding light into innate immune mechanisms involved in recognition of cell death.
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Abdul, Zani Izma 'Izzah Nadhirah. "Lectin-like oxidised low density lipoprotein 1 scavenger receptor regulation of signal transduction in cell function and atherosclerosis". Thesis, University of Leeds, 2017. http://etheses.whiterose.ac.uk/18113/.
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Since the discovery of the lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) by Sawamura and colleagues in 1997, this multi-ligand receptor has been implicated in atherosclerosis and diabetes. Oxidised LDL binding and trafficking via LOX-1 cause the activation of downstream signal transduction that cause pro-athrogenic changes such as endothelial dysfunction, apoptosis and foam cell formation. However, the molecular mechanisms have not be been fully explained. In this study, tetracycline- inducible cell lines expressing LOX-1 wild-type and trafficking-defective LOX-1-D5A were developed. The findings show different trafficking properties between LOX-1-WT and LOX-1-D5A in response to oxidised LDL. Due to these differences, LOX-1-WT and LOX-1-D5A in response to oxidised LDL exhibited differential downstream signal transduction. Moreover, 24 hour stimulation of oxidised LDL via LOX-1-WT caused decreased endothelial cell permeability; however, the underlying mechanism is not clear. The impact of deleting LOX-1 in ApoE knockout mice was reduced aortic plaque coverage. This study revealed that pro- atherogenic signal transduction was reduced in aorta in LOX-1/ApoE double knockout mice compared to ApoE knockout mice. Furthermore, the same pro-atherogenic signal transduction was increased in the liver of LOX-1/ApoE knockout mice. The differential signal transduction outcomes in the aorta or liver are dependent on the status of the atherosclerosis disease. LOX-1 is reported to play a role in glucose and lipid homeostasis. Previously, deleting LOX-1 revealed altered glucose metabolism and insulin resistance phenotype. In this study, differences in downstream insulin signalling pathways were exhibited in the skeletal muscle and adipose tissue of LOX-1 knockout and wild-type mice. Experimental findings also revealed the influence of LOX-1 genotype in iron metabolism in the liver. This work has provided insights on a potential role of LOX-1 clearing oxidised LDL from the circulation, and for the first time, this study potentially showed the role of LOX-1 in glucose homeostasis and iron metabolism.
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Inoue, Kazuhiko. "Overexpression of lectin-like oxidized low-density lipoprotein receptor-1 induces intramyocardial vasculopathy in apolipoprotein E-null mice". Kyoto University, 2006. http://hdl.handle.net/2433/144313.
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Ishikawa, Masahiro. "Lectin-like oxidized LDL receptor-1 signal is a potent biomarker and therapeutic target for human rheumatoid arthritis". Kyoto University, 2012. http://hdl.handle.net/2433/157433.
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Aramaki, Yo. "Lectin-like oxidized LDL receptor-1 (LOX-1) acts as a receptor for remnant-like lipoprotein particles (RLPs) and mediates RLP-induced migration of vascular smooth muscle cells". Kyoto University, 2008. http://hdl.handle.net/2433/124233.
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Raziunaite, Ingrida. "Use of C-type lectin receptor probes and human monoclonal antibodies to map the dynamics of the fungal cell wall". Thesis, University of Aberdeen, 2018. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=238675.
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Nakagawa, Takefumi. "Lectin-like oxidized low-density lipoprotein receptor 1 mediates leukocyte infiltration and articular cartilage destruction in rat zymosan-induced arthritis". Kyoto University, 2003. http://hdl.handle.net/2433/148464.
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Lorenz, Viola [Verfasser], e Bernhard [Gutachter] Nieswandt. "Cellular regulation of the hemITAM-coupled platelet receptor C-type lectin-like receptor 2 (CLEC-2): In vitro and in vivo studies in mice / Viola Lorenz ; Gutachter: Bernhard Nieswandt". Würzburg : Universität Würzburg, 2018. http://d-nb.info/1163536202/34.
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Straßer, Andreas Dominikus [Verfasser], Jürgen [Akademischer Betreuer] Ruland e Bernhard [Akademischer Betreuer] Küster. "Analysis of C-type lectin receptor induced NF-kappaB signaling / Andreas Dominikus Straßer. Gutachter: Bernhard Küster ; Jürgen Ruland. Betreuer: Jürgen Ruland". München : Universitätsbibliothek der TU München, 2014. http://d-nb.info/1052097340/34.
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Raulf, Marie-Kristin [Verfasser], Christina [Akademischer Betreuer] Strube, Bernd [Akademischer Betreuer] Lepenies, Maren von [Akademischer Betreuer] Köckritz-Blickwede e Minka [Akademischer Betreuer] Breloer. "C-type lectin receptor recognition in parasitic infections / Marie-Kristin Raulf ; Christina Strube, Bernd Lepenies, Maren von Köckritz-Blickwede, Minka Breloer". Hannover : Stiftung Tierärztliche Hochschule Hannover, 2021. http://d-nb.info/1237684927/34.
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Suwannasual, Usa. "Investigating the Mechanisms involved in Traffic-Generated Air Pollution–Mediated Disruption of the Blood-Brain Barrier in a Wild Type Mouse Model using a Pharmaceutical Intervention Approach". Thesis, University of North Texas, 2020. https://digital.library.unt.edu/ark:/67531/metadc1707379/.
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This study investigated whether oxLDL and/or angiotensin (Ang) II signaling pathways mediate traffic-generated air pollution- exposure induced alterations in blood-brain barrier (BBB) integrity and permeability in a healthy wild type (C57Bl/6) mouse model; additionally, whether these outcomes are exacerbated by a high fat-diet investigated. An environmentally relevant concentration of a mixture of vehicle engine exhaust (MVE) was used. To investigate the hypotheses, 12 wk old male C57Bl/6 mice on either a high fat (HF) or low fat (LF) diet were randomly assigned to inhalational exposure of either filtered-air (FA) or 30 µg PM/m3 diesel exhaust + 70 µg PM/m3 gasoline exhaust (MVE) for 6 hr/day for 30 days. Additionally, we examined mechanisms involved in MVE-mediated alterations BBB integrity using a novel BBB co-culture in vitro model, consisting of mouse primary cerebral vascular endothelial cells on an apical transwell and astrocytes in the basal compartment, which was treated with plasma from the mice on our exposure study. Our in vivo exposure study results showed that MVE inhalation resulted in increased circulating plasma oxLDL and Ang II, compared to FA controls. Additionally, we observed increased cerebral microvascular expression of oxLDL receptors, LOX-1 and CD-36, and Ang II receptor subtype 1 (AT1) in MVE-exposed C57Bl/6 mice, which was further exacerbated with consumption of an HF diet. Increased signaling of both Ang II and oxLDL was associated with decreased BBB integrity, as evidenced by the concurrent reduction in expression of tight junction (TJ) protein claudin-5 and increased permeability of sodium fluorescein (Na-F) from the blood into the cerebral parenchyma. Our results suggest that possible mechanisms involved in oxLDL and/or Ang II-mediated alterations in BBB integrity include oxidative stress and upregulated expression and activity of matrix metalloproteinase (MMP)-9, which is associated with degradation of TJ proteins in the BBB. Our in vitro BBB co-culture results confirm our in vivo findings, as we observe increased BBB permeability (TEER) and decreased integrity (decreased expression of TJ proteins) in the endothelial (apical) layer when treated with plasma from MVE-exposed mice, which was further exacerbated when treated with plasma from MVE-exposed mice on an HF diet. Pre-treatment of the endothelial cells with the AT1 receptor antagonist, Losartan, prior to applying plasma, resulted in attenuation of the alterations observed in endothelial integrity in the BBB co-culture treated with plasma from either MVE+LF or MVE+HF animals. These results suggest Ang II – AT1 signaling mediate, at least in part, the alterations in the BBB integrity observed after exposure to MVE. Moreover, we observed that treatment of the endothelial (apical) layer with plasma from MVE-exposed animals resulted in increased production of inflammatory mediators interleukin-6 (IL-6) and transforming growth factor-β in the astrocyte media (basal compartment). Additionally, these same astrocytes also displayed increased production of angiotensin-converting enzyme (ACE) and also AT1 receptor mRNA expression, while showing decreased expression of the aryl hydrocarbon receptor (AhR) and glutathione peroxidase (GPx). Collectively, these results suggest that exposure to the ubiquitous environmental air pollutant, vehicle engine emissions, results in increased oxLDL and Ang II signaling in the cerebral microvasculature, which is associated with decreased vessel integrity and increased oxidative stress and inflammatory signaling in the CNS. The observed detrimental outcomes are even further exacerbated when coupled with the consumption of an HF diet.
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Andreev, Darja [Verfasser], Aline [Akademischer Betreuer] Bozec e Falk [Gutachter] Nimmerjahn. "The impact of the C-type lectin receptor Mincle on osteoclast-mediated bone remodeling / Darja Andreev ; Gutachter: Falk Nimmerjahn ; Betreuer: Aline Bozec". Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2020. http://d-nb.info/1222739461/34.
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Kakinuma, Takumi. "Lectin-like oxidized low-density lipoprotein receptor 1 mediates matrix metalloproteinase 3 synthesis enhanced by oxidized low-density lipoprotein in rheumatoid arthritis cartilage". Kyoto University, 2005. http://hdl.handle.net/2433/144463.
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Chigusa, Yoshitsugu. "Reduced ABCA1 expression and low Nrf2 activation due to decreased lectin-like oxidized LDL receptor 1 (LOX-1)in the placenta are involved in preeclampsia". Kyoto University, 2014. http://hdl.handle.net/2433/188637.
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Bulteau, François. "Ciblage in vivo des tumeurs via l'antigène Tn : Développement d'un cluster de Macrophage Galactose Lectine Human Macrophage Galactose-Type Lectin (MGL) Recognizes the Outer Core of Escherichia coli Lipooligosaccharide". Thesis, Université Grenoble Alpes, 2020. http://www.theses.fr/2020GRALV048.
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L’ensemble des cellules, qu’elles soient procaryotes ou eucaryotes, est doté d’une couche de glycosylation externe riche et diversifiée, composant la face dominante immédiate en relation à leur environnement. Elles résultent de processus enzymatiques complexes liant les sucres entre eux et sur des protéines ou lipides. Des variations du « glycome » peuvent apparaître dans certaines pathologies. Les cancers sont les pathologies les plus fréquentes présentant des anomalies de ces glycosylations. Ces altérations sont quasi systématiques à la surface des cellules cancéreuses. Parmi celles-ci, l’antigène Thomsen-nouveau (Tn), un N-acétylgalactosamine (GalNAc) sur une sérine ou une thréonine, est fortement exprimé dans 90% des carcinomes mammaires ainsi que dans les cancers de la vessie, du col de l’utérus, de l’ovaire, du colon, de l’estomac et de la prostate. L’omniprésence de l’antigène Tn dans de nombreux cancers, associés à son absence dans les cellules saines, en fait une cible de choix pour la thérapie ciblée ou des vaccins synthétiques antitumoraux. Aucun anticorps ciblant l’antigène Tn n’est à ce jour disponible du fait de la difficulté à développer un anticorps avec une telle spécificité. Ainsi, nous nous sommes intéressés à une autre stratégie de ciblage, basée sur l’utilisation d’une molécule capable de reconnaître l’antigène Tn. Les lectines de type C sont une famille de protéines capables de se lier spécifiquement et de façon réversible à certains glucides, en présence de calcium. La macrophage galactose lectine (MGL) est une lectine de type C ayant une affinité très importante pour le GalNac et ses dérivés comme l’antigène Tn. Ce travail a consisté, dans un premier temps, à l’utilisation d’une forme recombinante soluble de la MGL pour valider le potentiel de cet outil pour le ciblage des cellules cancéreuses. Les différentes expériences, in vitro et in vivo, impliquant la MGL, ont démontré la capacité de cette dernière à cibler spécifiquement les tumeurs humaines via l’antigène Tn. La partie extracellulaire de la MGL est de ce fait un très bon candidat de vecteur pour le diagnostic et l’imagerie de tumeurs humaines et potentiellement pour l’administration de médicaments. Dans un deuxième temps, diverses stratégies de développement d’un outil bifonctionnel exploitant cette lectine ont été exploré. Le but était de créer une plateforme peptidique fonctionnalisable d’une part avec plusieurs domaines lectines, afin de contrôler l’affinité de reconnaissance, et d’autre part des groupements fonctionnels variable selon l’application recherché (diagnostique, thérapeutique, ...). Les différentes stratégies de couplage employées nous ont permis d’accrocher plusieurs CRD de lectine sur un support peptidique, cela en conservant l’état tridimensionnel et fonctionnel des protéines. Les caractérisations effectuées démontrent une importante augmentation de l’affinité directement fonction du nombre de lectine ajouté sur la plateforme. Ce travail ouvre la voie vers de nouveaux systèmes de ciblage des sucres modulable à façonAll cells, whether prokaryotic or eukaryotic, have a rich and diversified external glycosylation layer, forming the immediate dominant face in relation to their environment. They result from complex enzymatic processes linking sugars to each other and to proteins or lipids. Variations of the "glycome" can appear in certain pathologies. Cancers are the most frequent pathologies with abnormalities in these glycosylations. These alterations are almost systematic on the surface of cancer cells. Among them, the Thomsen-new antigen (Tn), an N-acetylgalactosamine (GalNAc) on a serine or threonine, is strongly expressed in 90% of mammary carcinomas as well as in cancers of the bladder, cervix, ovary, colon, stomach and prostate. The ubiquitous presence of the Tn antigen in many cancers, combined with its absence in healthy cells, makes it a target of choice for targeted therapy or synthetic anti-tumor vaccines. No antibody targeting the Tn antigen is currently available because of the difficulty in developing an antibody with such specificity. Thus, we were interested in an alternative targeting strategy, based on the use of a molecule capable of recognizing the Tn antigen. C-Type lectins are a family of proteins capable of specifically and reversibly binding to certain carbohydrates in the presence of calcium. Macrophage galactose lectin (MGL) is a C-type lectin with a high affinity for GalNac and its derivatives such as the Tn antigen. This work consisted, initially, in the use of a soluble recombinant form of MGL to validate the potential of this tool for the targeting of cancer cells. The different experiments, in vitro and in vivo, involving MGL, demonstrated the latter's ability to specifically target human tumors via the Tn antigen. The extracellular portion of MGL is therefore a very good vector candidate for the diagnosis and imaging of human tumors and potentially for drug delivery. In a second step, various strategies for the development of a bifunctional tool exploiting this lectin were explored. The goal was to create a peptide platform that could be functionalized on one hand with several lectin domains, in order to control recognition affinity, and on the other hand with functional groups that could be variable according to the application (diagnostic, therapeutic, ...). The different coupling strategies employed allowed us to attach several lectin CRDs to a peptide support, while preserving the three-dimensional and functional state of the proteins. The characterizations carried out show a significant increase in affinity directly related to the number of lectins added to the platform. This work paves the way to new customizable sugar-targeting systems
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Blot, Lauriane. "Rôle de CLEC12B dans l'immunité de la peau". Electronic Thesis or Diss., Université Côte d'Azur, 2023. https://intranet-theses.unice.fr/2023COAZ6034.
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CLEC12B a été identifié pour la première fois comme étant un récepteur inhibiteur exprimé par les cellules myéloïdes qui neutralise la cytotoxicité médiée par les cellules NK. CLEC12B est un récepteur de lectine de type C (CLR) possédant un domaine ITIM, mais dont la signalisation en aval et le ou les ligands restent en grande partie inconnus. Au cours des 30 dernières années, une fonction de présentation d'antigène des mélanocytes a émergé en raison de leur nature dendritique, de leur position stratégique dans la peau et de leur capacité phagocytaire. Dans un contexte de vitiligo, notre équipe a montré que l'activation de CXCR3B, le récepteur des chimiokines immunitaires CXCL9, CXCL10 et CXCL11, induit l'apoptose des mélanocytes humains en culture. Les mélanocytes restants, activés par la production d'IFNγ, expriment des marqueurs de costimulation, déclenchant ainsi la prolifération des lymphocytes T et l'immunité anti-mélanocytaire qui en résulte. De récents résultats de notre équipe ont montré que CLEC12B est principalement exprimé par les mélanocytes humains et joue un rôle important dans la régulation de la pigmentation cutanée, mais également dans la prolifération du mélanome.Dans ce projet, nous avons cherché à déterminer le rôle de CLEC12B dans l'immunité de la peau en utilisant des mélanocytes humains primaires provenant de donneurs sains. Nous démontrons ici que CLEC12B est essentiel à la production d'IFNγ et des chimiokines innées CXCL9, CXCL10 et CXCL11 par les mélanocytes, comme le montre la modulation de l'expression de CLEC12B à l'aide de techniques de surexpression ou d'extinction génique. Cette régulation se fait via la phosphorylation du domaine ITIM de CLEC12B, comme le montre la forme mutée du gène CLEC12B. De plus, CLEC12B peut non seulement moduler la production de chimiokines mélanocytaires, mais il est également capable d'augmenter directement le chimiotactisme des cellules immunitaires de la peau et donc de déclencher une immunité adaptative à long terme. D'un point de vue signalisation, nous montrons que CLEC12B module la voie de signalisation de l'IFNγ via l'axe STAT1/IRF1. De plus, CLEC12B potentialise l'effet de l'IFNγ dans les mélanocytes activés, induisant ainsi une plus grande production de chimiokines innées et in fine une plus grande chimio-attraction des cellules immunitaires. Nous avons également démontré que CLEC12B interagit directement avec Staphylococcus aureus et Escherichia coli et module une réponse immunitaire innée contre ces bactéries opportunistes présentes sur la peau via l'axe STAT1/IRF1/CXCL9. Enfin, nous avons montré que CLEC12B détecte des motifs présents sur les mélanocytes, les fibroblastes et les macrophages pro- et anti-inflammatoires, mais son ou ses ligands restent encore à être identifiés. Dans l'ensemble, ces résultats démontrent que CLEC12B est un acteur important dans l'immunité cutanée innée en modulant la production d'IFNγ et de chimiokines immunitaires, mais également dans l'immunité adaptative en modulant le chimiotactisme des cellules immunitaires via la phosphorylation de son domaine ITIM. Ce mécanisme présente un grand intérêt car l'IFNγ et le recrutement de cellules immunitaires sont des étapes initiales clés impliquées dans l'inflammation de nombreuses pathologies de la peau, faisant de ce récepteur une cible thérapeutique intéressante pour le traitement de maladies infectieuses, des troubles cutanés inflammatoires et pigmentaires, ainsi que du cancer ; tout cela pouvant être directement immuno-régulé par CLEC12B dans les mélanocytes. Cette nouvelle perspective prometteuse reste encore à être testée dans de futures étudesCLEC12B was first identified as an inhibitory receptor on myeloid cells that counteracts NK cells-mediated cytotoxicity. CLEC12B is a C-type Lectin Receptor (CLR) which possesses an ITIM domain, but ligand and downstream signaling are largely unknown. Over the past 30 years, an antigen-presenting function of melanocytes has emerged due to their dendritic nature, their strategic position in the skin and their phagocytic capacity. In a vitiligo context, our team has shown that CXCR3B activation, the receptor for immune chemokines CXCL9, CXCL10 and CXCL11, induces apoptosis of cultured human melanocytes. The remaining melanocytes, activated by the IFNγ production, express co-stimulatory markers which trigger T cell proliferation and subsequent anti-melanocytic immunity. Recent results from our team have shown that CLEC12B is mainly expressed in human melanocytes and plays an important role in the regulation of skin pigmentation, but also in melanoma proliferation.In this project, we set out to determine the role of CLEC12B in skin immunity using primary human melanocytes from healthy donors. We demonstrate that CLEC12B is critical in production of IFNγ and innate chemokines CXCL9, CXCL10 and CXCL11 by melanocytes, as shown by our regulation of CLEC12B expression using silencing or overexpression techniques. This regulation was driven by the phosphorylation of CLEC12B's ITIM domain as shown using CLEC12B mutated form of the gene. Furthermore, not only can CLEC12B drive melanocyte chemokine production, but it is also capable of directly increase chemoattraction of immune cells in the skin and therefore trigger a long-term adaptative immunity. From a signaling point of view, we show that CLEC12B modulates IFNγ signaling pathway through the STAT1/IRF1 axis. Moreover, CLEC12B potentiates the effect of IFNγ in primed melanocytes, thus inducing a larger production of innate chemokines and subsequent greater chemoattraction of immune cells. In addition, we have demonstrated that CLEC12B directly interacts with Staphylococcus aureus and Escherichia coli and modulates an innate immune response against these opportunistic bacteria found on the skin through the STAT1/IRF1/CXCL9 axis. Finally, we have shown that CLEC12B senses motifs present on melanocytes, fibroblasts, and both pro- and anti-inflammatory macrophages, but its exact ligand(s) still remains to be identified. Together, these results demonstrate that CLEC12B is an important player in innate skin immunity by modulating the production of IFNγ and immune chemokines, and in adaptative immunity by modulating the migration ability of immune cells through the phosphorylation of its ITIM domain. This mechanism is of great interest as IFNγ and cellular recruitment are key initial steps involved in inflammation of many skin pathologies, making this receptor an interesting therapeutic target for the treatment of infectious diseases, inflammatory and pigmentary skin disorders, as well as cancer; all which may be able to be directly immuneregulated by CLEC12B on melanocytes. This exciting novel prospect remains to be tested in future studies
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Wojitani, Maria Dulce Caoro Horie. "Avaliação da frequência do polimorfismo nos genes que codificam a lecitina ligadora da manose (MBL) e o antagonista do receptor da interleucina-1 (IL1-Ra) em mulheres portadoras de candidíase vulvovaginal recorrente". Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5139/tde-23082011-135628/.
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A candidíase vulvovaginal corresponde a uma das mais frequentes infecções do trato reprodutivo. Estima-se que 75% das mulheres na idade reprodutiva experimentarão pelo menos um episódio de candidíase vulvovaginal durante suas vidas, a maioria evoluirá com episódios infrequentes, entretanto, 5% sofrerão recorrência, ou seja, quatro ou mais episódios de candidíase vulvovaginal comprovadas clínica e laboratorialmente no período de 1ano. Os mecanismos pelos quais as recorrências ocorrem ainda são pouco conhecidos, estando provavelmente relacionados à alterações na imunidade local. O presente estudo teve como objetivo avaliar as associações entre os polimorfismos nos genes que codificam a lecitina ligadora de manose (MBL) e do antagonista do receptor da interleucina 1 (IL1-Ra) com a candidíase vulvovaginal recorrente (CVVR) em mulheres brasileiras. Foram estudadas 100 mulheres portadoras de CVVR atendidas no Serviço de Imunologia Genética e Infecções do Trato Reprodutivo da Disciplina de Ginecologia da Faculdade de Medicina da Universidade de São Paulo. Para a análise dos polimorfismos nos genes que codificam para a MBL e o IL1-Ra realizou-se coleta de células bucais que foram enviadas para Division of Immunology and Infectious Diseases of Weill Medical College of Cornell University Resultados: Mulheres com candidíase vulvovaginal recorrente apresentaram maior frequência de polimorfismo no códon 54 do gene que codifica a MBL quando comparadas a mulheres saudáveis. Não foram observadas diferenças estatisticamente significativas na frequência do polimorfismo do gene que codifica o IL1-Ra entre os grupos estudadosVulvovaginal candidiasis is the most common genital infection in women during their childbearing years. About 75% of women suffer at least one syntomatic episode during their lives. Most of them will have infrequent episodes, but 5% will suffer recurrent episode of vulvovaginal candidiasis. The mechanisms responsible for recurrent vulvovaginal candidiasis (RVCC) remain a matter of speculation, although an alteration in local immunity appears to be a major factor. The aim of this study was to assess the correlation between polymorphisms in the genes coding for mannose-binding lectin (MBL) and interleukin-1 receptor antagonist (IL1-Ra) and RVCC in women from São Paulo, Brazil. The study population consisted of 100 women with RVCC, who were seen at Serviço de Infecções do Trato Reprodutivo da Disciplina de Ginecologia da Faculdade de Medicina da Universidade de São Paulo. To analyse for the MBL códon 54 gene polymorphism and for IL1-Ra, buccal cells were obtained with a cotton swabs and shipped to New York at ambient temperature. The polymorphisms were identified in the Division of Immunology and Infectious Diseases of Weill Medical College of Cornell University. Results: Women with RVVC present a high frequency of polymorphisms at codon 54 in the gene coding for MBL; on the other hand there were no differences in polymorphism frequency in the gene coding for IL1-Ra when compared to control women
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Lo, Tsun Ho. "A Study on the C-Type Lectin Receptor CD302 Reveals a Role in Dendritic Cell Migration and Its Potential as A Therapeutic Target for Acute Myeloid Leukaemia". Thesis, The University of Sydney, 2018. http://hdl.handle.net/2123/18582.
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C-type lectin receptors (CLR) play important roles in immune cell interactions with the environment. We described CD302 as the simplest type I CLR, which is restricted to myeloid cells in human blood. CD302 colocalised with cell migratory structures including podosomes and lamellopodia, leading us to hypothesise that this CLR contributes to cell migration. This thesis describes the use of mouse models to obtain further insights into CD302 expression and immunological function. Akin to humans, mouse CD302 transcripts were highest in liver, lungs, lymph nodes (LN), spleen, and bone marrow. Detailed analysis of CD302 transcription in immune cells revealed high expression by macrophage (Mϕ), granulocytes and myeloid dendritic cells (mDC). Greater CD302 expression was found in migratory compared to resident mDC. We generated the first CD302 knockout (CD302KO) mouse and revealed a decrease in migratory mDC within LN of these animals. CD302KO migratory DC exhibited reduced in vivo migration into LN interfollicular channels, establishing a role for CD302 in mDC migration. CD169+ Mϕ in LN subcapsular sinus also showed irregular distribution. Monoclonal antibodies have been shown effective in the treatments of different haematological malignancies. However, acute myeloid leukaemia (AML) targets are currently limited so discovery of new targets would be beneficial to patients. We found expression of CD302 on the surface of blasts in the vast majority of AML patients. More importantly, CD302 was positive on leukaemic stem cells, the population responsible for relapse of the disease. Monoclonal antibodies targeting human CD302 were effective in mediating antibody dependent cell cytotoxicity and were internalised, making them amenable to toxin conjugation. Targeting CD302 with antibodies also limited in vivo engraftment of the leukaemic cell line HL-60 in NOD/SCID mice. These studies provide the foundation for studies examining CD302 as a potential therapeutic target for AML.
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Hayashida, Kazutaka. "Lectin-like oxidized LDL receptor-1 (LOX-1) supports adhesion of mononuclear leukocytes and a monocytic-like cell line THP-1 cells under static and flow conditions". Kyoto University, 2003. http://hdl.handle.net/2433/148700.
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May, Frauke [Verfasser], e Bernhard [Akademischer Betreuer] Nieswandt. "The role of the (hem)ITAM-coupled receptors C-type lectin-like receptor 2 (CLEC-2) and Glycoprotein (GP) VI for platelet function: in vitro and in vivo studies in mice / Frauke May. Betreuer: Bernhard Nieswandt". Würzburg : Universitätsbibliothek der Universität Würzburg, 2013. http://d-nb.info/103731140X/34.
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Wessels, Miriam [Verfasser]. "The intracellular lectin vesicular integral-membrane protein (VIP36) as a potential sorting receptor for the glycoproteins dipeptidyl peptidase IV and sucrase-isomaltase in the early secretory pathway / Miriam Wessels". Hannover : Technische Informationsbibliothek und Universitätsbibliothek Hannover (TIB), 2011. http://d-nb.info/1013471717/34.
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Niveau, Camille. "Impact des glycans tumoraux sur les propriétés phénotypiques, fonctionnelles et métaboliques des cellules dendritiques (cDC2, pDC, cDC1) humaines en contexte de mélanome". Electronic Thesis or Diss., Université Grenoble Alpes, 2024. http://www.theses.fr/2024GRALV022.
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Les cellules dendritiques (DCs), comprenant les cDC2s BDCA1+, les cDC1s BDCA3+ et les pDCs BDCA2+ sont les chefs d’orchestre des réponses immunitaires. Leur plasticité joue un rôle crucial dans l’orientation des réponses immunitaires, notamment en contexte de cancer. Cependant, l’échappement à la surveillance immunitaire est une étape essentielle dans le développement des tumeurs. En contexte de mélanome, les DCs trouvées dans la tumeur ont une fonctionnalité altérée, influençant négativement l’évolution clinique des patients. Les mécanismes employés par le mélanome pour moduler l’immunité ne sont que partiellement élucidés. L’immuno-métabolisme émerge comme un facteur décisif pour l’orientation des réponses immunes en contexte de cancer. Parallèlement, les cellules tumorales présentent à leur surface une glycosylation aberrante des protéines et lipides qui peut être reconnue par les lectines, récepteurs exprimés par les DCs. Parmi eux, les récepteurs lectines de type C (CLR) sont cruciaux pour la plasticité des DCs et le façonnement des réponses immunitaires, et leur expression est perturbée sur les DCs des patients mélanome. De plus, le glycocode des cellules tumorales de mélanome est corrélé avec la fonction des DCs et l’évolution clinique des patients. Néanmoins, l’impact des différents motifs de glycosylation dans le mélanome sur le phénotype, la fonction et le métabolisme des DCs n’est pas connu.Nous avons étudié les interactions des sous-types de DCs avec six glycans présents à la surface des cellules de mélanome (Gal, Man, GalNAc, s-Tn, Fuc, GlcNAc). Nous avons analysé l’impact de ces glycans sur le phénotype (état d’activation, points de contrôle immunitaires (ICP)) et la fonction (cytokines/chimiokines) des DCs. Afin de mieux comprendre la dérégulation de la fonction des DCs dans le mélanome, nous avons exploré leur métabolisme chez les patients grâce à la technique SCENITH, et mis en relation leur profil métabolique avec leur phénotype, leur fonction et l’évolution clinique des patients. Nous avons aussi évalué l’impact des cellules tumorales et du glycocode sur le métabolisme des DCs, et évalué la possibilité de moduler les voies métaboliques afin de réverser l’impact des glycans sur la fonction des DCs.Les DCs sont capables d’interagir avec et d’internaliser les glycans étudiés, à différentes intensités selon le sous-type de DCs et la nature du glycan. Le fucose induit un remodelage de l’expression des ICPs et une augmentation des molécules d’activation, et provoque la sécrétion de cytokines/chimiokines associées à l’inflammation et à la progression tumorale. Après activation des DCs, leur sécrétome est complètement remodelé par l’exposition aux glycans, particulièrement avec le fucose. Parallèlement, nous avons mis en évidence des perturbations métaboliques majeures des DCs dans le sang et la tumeur des patients mélanome par rapport aux donneurs sains. L’expression de marqueurs d’activation et d’ICPs par les DCs ainsi que l’évolution clinique des patients sont liés au profil métabolique des DCs. De plus, le métabolisme des DCs en co-culture avec des cellules de mélanome est corrélé avec l’expression de certains glycans tumoraux. En accord avec ces résultats, les glycans étudiés modulent directement le métabolisme des DCs en plus de leur phénotype et de leur fonction. Le blocage du transporteur de lactate MCT-1 permet de restaurer la fonctionnalité des DCs altérée par les glycans.Cette étude révèle l’importance des motifs glycosylés dans la modulation et la régulation des DCs. L’axe glycan-lectine-DC émerge comme un nouveau point de contrôle immunitaire dans le mélanome, lié au métabolisme et qui pourrait permettre la restauration de l’immunité anti-tumorale en empêchant les interactions des DCs avec les glycans ou en modulant leur métabolisme. Cet axe ouvre la voie au développement de nouvelles stratégies thérapeutiques afin d’améliorer l’évolution clinique des patients atteints de mélanomeDendritic cells (DCs), mostly consisting of BDCA1+ cDC2s, BDCA3+ cDC1s, and BDCA2+ pDCs are the conductors of immune responses. Their plasticity plays a crucial role in the orientation of immune responses, especially in the context of cancer. However, escape from immune surveillance is a key step for tumor development. In the context of melanoma, tumor-infiltrating and circulating DCs harbor an altered functionality, negatively linked with the clinical outcome of patients. The mechanisms employed by melanoma to modulate immunity are only partially deciphered. Immuno-metabolism emerges as a decisive factor for the orientation of immune responses in cancer. In parallel, tumor cells display aberrant glycans on surface protein and lipids that can be recognized by lectin receptors, expressed by DCs. Among them, C-type lectin receptors (CLRs) are crucial for DCs’ plasticity and the modeling of immune responses, and their expression is perturbed on DCs from melanoma patients. In addition, the tumor cells’ glycocode correlates with DC function and clinical outcome of patients. Nevertheless, influence of the various glycosylation motifs on immunity remains unknown in melanoma.We investigated the interactions of DC subsets with six glycans present on the surface of melanoma tumor cells (Gal, Man, GalNAc, s-Tn, Fuc, GlcNAc). We analyzed the effect of these glycans on the phenotype (activation status, immune checkpoints (ICP)), and the function (cytokines/chemokines) of DCs. In order to better understand DCs dysregulation in melanoma, we explored their metabolism among patients thanks to the SCENITH technique, and analyzed the correlation with their phenotype, their function and the clinical outcome of patients. We also assessed the impact of tumor cells and their glycocode on DCs’ metabolism, and we evaluated the possibility to modulate metabolic pathways with the aim of reverting the impact of glycans on DCs’ function.DCs are able to interact with and to internalize the studied glycans, at different intensities according to the DC subset and to the nature of the glycan. Fucose induces a remodeling of ICP expression and increases activation molecules, in addition to trigger the secretion of pro-inflammatory and pro-tumoral cytokines/chemokines. After activation, DC’s secretome is completely reshaped by glycan exposure, particularly with fucose. In parallel, we highlight major metabolic disturbances in DCs from patients’ blood and tumor compared to healthy donors. The expression of activation markers and ICPs by DCs as well as the clinical outcome of patients are linked with the metabolic profile of DCs. Moreover, DCs’ metabolism in co-culture with melanoma cells correlates with the expression of particular tumor glycans. Coherently, the studied glycans directly modulate DCs’ metabolism in addition to their phenotype and function. The blockade of the MCT-1 lactate transporter allows restoring DCs’ function altered by glycans.This study unveils the importance of glycan motifs in the modulation and regulation of DCs. The glycan-lectin-DC axis emerges as a new immune checkpoint in melanoma, linked with metabolism, and which could enable the restoration of anti-tumor immunity by preventing DC-glycan interactions or by acting on their metabolism. This axis opens the way for the development of new therapeutic strategies with the aim of improving clinical success for melanoma patients
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Lindenwald, Dimitri Leonid [Verfasser], Bernd [Akademischer Betreuer] Lepenies, Silke [Akademischer Betreuer] Rautenschlein, Roland [Akademischer Betreuer] Lang e Tina Sørensen [Gutachter] Dalgaard. "Veterinary Glycoimmunology: Generation and in vitro application of a novel sheep C-type lectin receptor fusion protein library / Dimitri Leonid Lindenwald ; Gutachter: Tina Sørensen Dalgaard ; Bernd Lepenies, Silke Rautenschlein, Roland Lang". Hannover : Stiftung Tierärztliche Hochschule Hannover, 2020. http://d-nb.info/1224882903/34.
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Monteiro, João Gonçalo Tereno Verfasser], Bernd [Akademischer Betreuer] [Lepenies, Ralph Akademischer Betreuer] Goethe e Reinhard [Akademischer Betreuer] [Schwartz-Albiez. "A C-type lectin receptor (CLR)-Fc fusion protein library as a toolbox to detect novel CLR ligands and the interplay of CLR/virus interactions / João Gonçalo Tereno Monteiro ; Bernd Lepenies, Ralph Goethe, Reinhard Schwartz-Albiez". Hannover : Stiftung Tierärztliche Hochschule Hannover, 2019. http://d-nb.info/119175278X/34.
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Monteiro, João Gonçalo Tereno [Verfasser], Bernd [Akademischer Betreuer] Lepenies, Ralph [Akademischer Betreuer] Goethe e Reinhard [Akademischer Betreuer] Schwartz-Albiez. "A C-type lectin receptor (CLR)-Fc fusion protein library as a toolbox to detect novel CLR ligands and the interplay of CLR/virus interactions / João Gonçalo Tereno Monteiro ; Bernd Lepenies, Ralph Goethe, Reinhard Schwartz-Albiez". Hannover : Stiftung Tierärztliche Hochschule Hannover, 2019. http://d-nb.info/119175278X/34.
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Mahrouf-Yorgov, Meriem. "Contribution à l'étude des propriétés vasculoprotectrices de la metformine : effets sur la voie de transduction de la protéine kinase C et sur le dysfonctionnement endothélial vasculaire du diabète". Paris 5, 2007. http://www.theses.fr/2007PA05P623.
Texto completo da fonteResumo:
Le diabète est un important problème de santé publique en raison des complications vasculaires qu’il engendre. Il a été montré que la metformine (met), biguanide très utilisé dans le traitement du diabète de type 2, possède des effets vasculoprotecteurs indépendants de son effet antihyperglycémiant. Dans ce travail nous avons recherché son effet sur l’activité de la protéine kinase C (PKC) et de la polyADP-ribose polymérase (PARP), deux voies de signalisation majeures activées par l’hyperglycémie et décrites comme étant très impliquées dans le développement des complications vasculaires des patients diabétiques. Nous avons également étudié l’effet de la met sur l’expression du récepteur (RAGE) des produits de glycation avancée et du récepteur des LDL oxydés (LOX-1), marqueurs du dysfonctionnement endothélial artériel liés à la macroangiopathie diabétique. Nos résultats nous ont permis de proposer un mécanisme d’action de la metformine dont le site initial se situe au niveau membranaireType 2 diabetes is an important public health problem due to vascular complications caused by chronic hyperglycemia. Hyperglycemia has been shown to induce intracellular formation of reactive oxygen species and causes oxidative stress leading to vascular dysfunction. Metformin (met) is a widely used drug for the management of type 2 diabetes. Several studies showed that met improves vascular function of diabetic patients but its exact mechanism of action remains unclear. We investigate in this study the effect of met on the protein kinase C (PKC) and polyADP-ribose polymerase (PARP) pathways involved in diabetic vascular complications. We also explored whether met could modulate the redox-sensible expression of advanced glycation end products receptor (RAGE) and lectin-like oxidized receptor 1 (LOX-1). Taken together our results suggests that met acts at the membrane level and we proposed a unifying mechanism by which metformin improves diabetic vascular endothelial functions
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Christou, Charita. "C-type lectin-like receptors and their interactions". Thesis, University of Oxford, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.509908.
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Tromans, Robert. "Urea based synthetic lectins : a biomimetic receptor for glucose". Thesis, University of Bristol, 2018. http://hdl.handle.net/1983/9d08416b-1317-419e-b95c-605020a9334d.
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The binding of polar organic molecules in water is one of the most difficult problems in molecular recognition. Carbohydrates are especially challenging targets, given their complex, hydromimetic and subtly variable structures. As a result, carbohydrate-binding proteins such as lectins often display low affinities and moderate selectivities, especially when compared to other classes of small molecule binding proteins. ‘Synthetic lectin’ mimics have been reported for several years, but have typically been still weaker, with previous approaches generally consisting of macrocycles employing aromatic surfaces bridged with amide bearing spacer units. This project aimed to investigate a new type of synthetic lectin employing bis-urea spacer units. Incorporation of this urea spacer design into anthracene tetraurea 1 afforded good affinities and selectivities, comparable to natural lectins, for cellodextrin oligosaccharide substrates (such as D-cellotriose 2). The potential of the urea spacer was fully realised when incorporated into triethylbenzene hexaurea 3 however, which shows binding affinities and selectivities for D-glucose 4 that far exceed any previous synthetic system. Receptor 3 even continues to function in complex biological media (such as human blood serum), enabling preliminary proof of concept for 3 acting as a D-glucose 4 sensor. The performance of 3 even surpasses most natural systems (such as lectins) and therefore can be considered the first true example of a synthetic biomimetic receptor for D-glucose.
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Barwell, Nicholas P. "Synthetic lectins : biomimetic receptors for carbohydrates in water". Thesis, University of Bristol, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.495920.
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Fournier, Nathalie. "Les familles de récepteurs à ITAM et à ITIM : caractérisation des molécules DCIR et FDF03 exprimées par les cellules dendritiques humaines". Lyon 1, 2000. http://www.theses.fr/2000LYO1T009.
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