Artículos de revistas: "Glandes submucosales"

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Melgarejo-Moreno, Pablo y Diego Hellin-Meseguer. "Different glycoconjugates in the submucosal glands of the supraglottis and subglottis. Lectin histochemistry study in the hamster". Journal of Laryngology & Otology 111, n.º 5 (mayo de 1997): 441–43. http://dx.doi.org/10.1017/s0022215100137582.

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AbstractA lectin histochemistry study was performed in the supraglottic and subglottic regions of 10 hamsters. The submucosal glands were observed by light microscopy. The supraglottic submucosal glands presented numerous mucous tubules but on the other hand, the subglottic submucosal glands had serous tubules which finished at the distal portion in serous acini. The results suggest that the distribution of fucosylatedmucin and serum-type glycloproteins between the supra- and subglottic submucosal glands suggest a different viscosity and function of the mucus.

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2

Hopwood, D., G. Coghill y D. S. A. Sanders. "Human oesophageal submucosal glands". Histochemistry 86, n.º 1 (1986): 107–12. http://dx.doi.org/10.1007/bf00492353.

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Somogyvári, Krisztina, Péter Móricz, Imre Gerlinger, László Kereskai, István Szanyi y Ildikó Takács. "Morphological and Histological Effects of Radiofrequency and Laser (KTP and Nd:YAG) Treatment of the Inferior Turbinates in Animals". Surgical Innovation 24, n.º 1 (13 de octubre de 2016): 5–14. http://dx.doi.org/10.1177/1553350616673452.

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The aim of this study was to evaluate the short and medium-term effects of radiofrequency (RF) and potassium titanyl phosphate (KTP) and neodymium-yttrium-aluminum garnet (Nd:YAG) laser treatment on the inferior turbinate mucosa in a porcine model. Following randomization, the inferior turbinates were treated either with RF submucosally or with the KTP or the Nd:YAG laser on the surface under videoendoscopic control. Tissue samples were taken at the end of postoperative weeks 1 and 6, and were evaluated macroscopically and histopathologically. Scanning electron microscopy was implemented to demonstrate the morphological changes in the respiratory epithelium. Six weeks following the RF procedure, the mucosa was intact in all cases, and the volume of the inferior turbinates was reduced in the majority of the cases. Although a volume reduction occurred in both laser groups, more complications associated with the healing procedure were noted. With hematoxylin and eosin and periodic acid–Schiff staining, intact epithelium, and submucosal glands remained after the RF procedures at the end of postoperative week 6. Following the KTP-laser intervention, necrotizing sialometaplasia and cartilage destruction occurred, and squamous metaplasia was also apparent in the Nd:YAG group. In both laser groups, dilated glands with excess mucus were seen. The scanning electron microscopic findings demonstrated that cilia were present in all cases. In conclusion, the medium-term macroscopic results were similar in all 3 groups, but the postoperative complications were less following the RF procedure. RF procedure is minimally invasive due to the submucosal intervention that leads to a painless, function preserving recovery.

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Moore, Beverley A., David Kim y Stephen Vanner. "Neural pathways regulating Brunner's gland secretion in guinea pig duodenum in vitro". American Journal of Physiology-Gastrointestinal and Liver Physiology 279, n.º 5 (1 de noviembre de 2000): G910—G917. http://dx.doi.org/10.1152/ajpgi.2000.279.5.g910.

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This study examined the neural pathways innervating Brunner's glands using a novel in vitro model of acinar secretion from Brunner's glands in submucosal preparations from the guinea pig duodenum. Neural pathways were activated by focal electrical stimulation and excitatory agonists, and videomicroscopy was used to monitor dilation of acinar lumen. Electrical stimulation of perivascular nerves evoked large dilations that were blocked by TTX (1 μM) or the muscarinic receptor antagonist 4-diphenylacetoxy- N-(2-chloroethyl)-piperidine hydrochloride (1 μM). The nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium iodide (100 μM) had no effect, and the nerve-evoked responses were not inhibited by hexamethonium (200 μM). Dilations were abolished in preparations from chronically vagotomized animals. Activation of submucosal ganglia significantly dilated submucosal arterioles but not Brunner's glands. Effects of electrical stimulation of perivascular and submucosal nerves were not altered by guanethidine. Capsaicin and substance P also dilated arterioles but had no effect on Brunner's glands. Cholinergic (choline acetyltransferase-immunoreactive) nerve fibers were found in Brunner's glands. These findings demonstrate that Brunner's glands are innervated by cholinergic vagal fibers but not by capsaicin-sensitive or intrinsic enteric nerves.

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5

Sasaki, T., S. Shimura, H. Sasaki y T. Takishima. "Effect of epithelium on mucus secretion from feline tracheal submucosal glands". Journal of Applied Physiology 66, n.º 2 (1 de febrero de 1989): 764–70. http://dx.doi.org/10.1152/jappl.1989.66.2.764.

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We studied the effect of airway epithelium on mucus secretion by use of an isolated tracheal submucosal gland preparation reported previously (J. Appl. Physiol. 60: 1237–1247, 1986). Mucus glycoconjugate release from submucosal glands of feline trachea was examined using [3H]glucosamine as a mucus precursor. Isolated glands showed significantly higher secretory responses to cholinergic, alpha-, and beta-adrenergic agonists and dibutyryladenosine 3′,5′-cyclic monophosphate (average 400% of control) than the conventional tracheal mucosal explants, which contained epithelium and submucosal tissues in addition to submucosal glands (average 160% of control). The addition of isolated epithelium depressed the secretory response of isolated glands to the same level as that of tracheal explants. However, the supernatant from isolated epithelium failed to inhibit secretory responses to methacholine in isolated glands, suggesting that the epithelium-derived inhibitory factor to secretion may be short-lived. Leukotriene D4 antagonist (FPL 55712), cyclooxygenase and/or lipoxygenase inhibitors (indomethacin or BW 755C) caused no significant change in the inhibitory action of epithelium, suggesting that the inhibition is not due to arachidonic acid metabolites. The newly found secretory inhibitory action of epithelium is of particular interest in the pathogenesis of hypersecretion associated with epithelial damage.

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Pilewski, J. M., J. F. Engelhardt, J. E. Bavaria, L. R. Kaiser, J. M. Wilson y S. M. Albelda. "Adenovirus-mediated gene transfer to human bronchial submucosal glands using xenografts". American Journal of Physiology-Lung Cellular and Molecular Physiology 268, n.º 4 (1 de abril de 1995): L657—L665. http://dx.doi.org/10.1152/ajplung.1995.268.4.l657.

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The cystic fibrosis (CF) transmembrane conductance regulator has been localized to both submucosal glands and surface epithelium, suggesting that both glandular and surface epithelium may be important targets for gene therapy. To determine the distribution and efficiency of recombinant adenovirus-mediated gene transfer to human airway submucosal glands, an in vivo model was developed by heterotopically transplanting human bronchial segments from both normal and CF lung tissue into severe combined immunodeficient mice. A serotype 5 E1-deleted recombinant adenovirus containing a lacZ reporter gene driven by the cytomegalovirus promoter (H5.010CMVlacZ) was used to infect the xenografts. Transgene expression was correlated with three factors: 1) viral titer, 2) penetration of microspheres, and 3) dwell time of the viral instillate. At viral titers ranging from 10(8) to 10(11) plaque forming units/ml, expression of the lacZ gene was observed in a subpopulation of epithelial cells within approximately 40% of submucosal glands, with more efficient gene transfer to the ducts than the secretory tubules. Within individual glands, gene transfer varied from < 1% to approximately 20% of submucosal cells, including duct, mucous, and serous cells. Adenovirus-sized fluorescent microspheres were found to penetrate only some of the submucosal glands, suggesting that the gene transfer efficiency to submucosal tubules is due to limited viral particle penetration rather than tropism. Gene transfer to surface epithelial cells was inefficient. However, the percentage of transduced surface epithelial cells increased from < 1% to 5–10% as the dwell time of viral solution was increased from 5 min to 1 h, indicating that the time allowed for virus binding and entry is important for gene transfer efficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

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7

Wine, J. J. "Submucosal Glands and Airway Defense". Proceedings of the American Thoracic Society 1, n.º 1 (1 de enero de 2004): 47–53. http://dx.doi.org/10.1513/pats.2306015.

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8

Baniak, Nicholas, Xiaojie Luan, Amber Grunow, Terry E. Machen y Juan P. Ianowski. "The cytokines interleukin-1β and tumor necrosis factor-α stimulate CFTR-mediated fluid secretion by swine airway submucosal glands". American Journal of Physiology-Lung Cellular and Molecular Physiology 303, n.º 4 (15 de agosto de 2012): L327—L333. http://dx.doi.org/10.1152/ajplung.00058.2012.

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The airway is kept sterile by an efficient innate defense mechanism. The cornerstone of airway defense is mucus containing diverse antimicrobial factors that kill or inactivate pathogens. Most of the mucus in the upper airways is secreted by airway submucosal glands. In patients with cystic fibrosis (CF), airway defense fails and the lungs are colonized by bacteria, usually Pseudomonas aeruginosa . Accumulating evidence suggests that airway submucosal glands contribute to CF pathogenesis by failing to respond appropriately to inhalation of bacteria. However, the regulation of submucosal glands by the innate immune system remains poorly understood. We studied the response of submucosal glands to the proinflammatory cytokines interleukin-1β and tumor necrosis factor-α. These are released into the airway submucosa in response to infection with the bacterium P. aeruginosa and are elevated in CF airways. Stimulation with IL-1β and TNF-α increased submucosal gland secretion in a concentration-dependent manner with a maximal secretion rate of 240 ± 20 and 190 ± 40 pl/min, respectively. The half maximal effective concentrations were 11 and 20 ng/ml, respectively. The cytokine effect was dependent on cAMP but was independent of cGMP, nitric oxide, Ca2+, or p38 MAP kinase. Most importantly, IL-1β- and TNF-α-stimulated secretion was blocked by the CF transmembrane conductance regulator (CFTR) blocker, CFTRinh172 (100 μmol/l) but was not affected by the Ca2+-activated Cl− channel blocker, niflumic acid (1 μmol/l). The data suggest, that during bacterial infections and resulting release of proinflammatory cytokines, the glands are stimulated to secrete fluid, and this response is mediated by cAMP-activated CFTR, a process that would fail in patients with CF.

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9

Eguchi, Koichi, Kunihiko Aoyagi, Satoshi Nimura y Shotaro Sakisaka. "Diagnostic Value of Endoscopic and Endoscopic Ultrasound Characteristics of Duodenal Submucosal Tumour-Like Heterotopic Gastric Mucosa". Canadian Journal of Gastroenterology 25, n.º 7 (2011): 365–67. http://dx.doi.org/10.1155/2011/104815.

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OBJECTIVE: Recent studies have reported that duodenal heterotopic gastric mucosa (HGM) has been observed in 8.9% of patients who undergo esophagogastroduodenoscopy. However, there are few reports concerning the endoscopic and endoscopic ultrasound characteristics of submucosal tumour-like HGM in the duodenum.METHODS: Endoscopic, endoscopic ultrasound (EUS) and histological findings were analyzed in six patients with submucosal tumour-like HGM, which were confirmed by pathological examination of biopsy or endoscopic polypectomy specimens.RESULTS: Endoscopically, the lesions appeared as a solitary, sessile submucosal tumour-like mass with a depression at the top. In four of six patients, small granular structures were found in the depressed area of the mass. On EUS, all masses demonstrated a heterogeneous pattern, among which four patients presented anechoic areas while two patients showed no anechoic areas. All lesions were localized within the mucosa and submucosa on EUS. Histologically, they consisted of gastric glands and some dilated glands, and were covered with normal duodenal epithelium. In four of six lesions, the tumours were composed of gastric-type foveolar epithelium showing papillary growth, fundic glands and pyloric glands, while the others consisted of gastric-type foveolar epithelium and pyloric glands.CONCLUSION: A heterogeneous pattern on EUS and small granular structures on esophagogastroduodenoscopy represent valuable diagnostic features of submucosal tumour-like HGM.

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10

Duan, D., Y. Yue, W. Zhou, B. Labed, T. C. Ritchie, R. Grosschedl y J. F. Engelhardt. "Submucosal gland development in the airway is controlled by lymphoid enhancer binding factor 1 (LEF1)". Development 126, n.º 20 (15 de octubre de 1999): 4441–53. http://dx.doi.org/10.1242/dev.126.20.4441.

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Previous studies have demonstrated that transcription of the lymphoid enhancer binding factor 1 (Lef1) gene is upregulated in submucosal gland progenitor cells just prior to gland bud formation in the developing ferret trachea. In the current report, several animal models were utilized to functionally investigate the role of LEF1 in initiating and supporting gland development in the airway. Studies on Lef1-deficient mice and antisense oligonucleotides in a ferret xenograft model demonstrate that LEF1 is functionally required for submucosal gland formation in the nasal and tracheal mucosa. To determine whether LEF1 expression was sufficient for the induction of airway submucosal glands, two additional model systems were utilized. In the first, recombinant adeno-associated virus was used to overexpress the human LEF1 gene in a human bronchial xenograft model of regenerative gland development in the adult airway. In a second model, the LEF1 gene was ectopically overexpressed under the direction of the proximal airway-specific CC10 promoter in transgenic mice. In both of these models, morphometric analyses revealed no increase in the number or size of airway submucosal glands, indicating that ectopic LEF1 expression alone is insufficient to induce submucosal gland development. In summary, these studies demonstrate that LEF1 expression is required, but in and of itself is insufficient, for the initiation and continued morphogenesis of submucosal glands in the airway.

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HOVENBERG, Hans W., Ingemar CARLSTEDT y Julia R. DAVIES. "Mucus glycoproteins in bovine trachea: identification of the major mucin populations in respiratory secretions and investigation of their tissue origins". Biochemical Journal 321, n.º 1 (1 de enero de 1997): 117–24. http://dx.doi.org/10.1042/bj3210117.

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Bovine respiratory secretions were separated into gel and sol phases to allow the identification of the gel-forming mucins. Mucins were subsequently isolated from the surface epithelium and submucosal tissue to investigate the tissue origins of the species in the secretions. Density-gradient centrifugation revealed ‘high-density’ and ‘low-density’ mucins in the gel phase of the secretions. The ‘high-density’ mucins were large, composed of subunits joined by disulphide bonds and contained two highly glycosylated domains of apparently different lengths, whereas the ‘low-density’ mucins were smaller and monomeric. The sol also contained both ‘high-density’ and ‘low-density’ species. A ‘high-density’ mucin similar to that in the gel was isolated from the surface epithelium, suggesting that the goblet cells produce large, gel-forming mucins. A second ‘high-density’ species was released from the submucosal tissue after reduction/alkylation, indicating that large mucins from the submucosal glands may also be a component of the mucus gel. In addition, two small, ‘low-density’ mucins were obtained from the submucosal tissue. One species was associated with the gel phase but was also present in the sol, whereas the other was present only in the sol. Bovine respiratory-tract secretions thus comprise a complex mixture of large gel-forming mucins originating from the goblet cells and submucosal glands, and smaller ‘soluble’ species from the submucosal glands which may interact with the gel.

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12

Van Seuningen, I., J. P. Audie, B. Gosselin, J. J. Lafitte y M. Davril. "Expression of human mucous proteinase inhibitor in respiratory tract: a study by in situ hybridization." Journal of Histochemistry & Cytochemistry 43, n.º 6 (junio de 1995): 645–48. http://dx.doi.org/10.1177/43.6.7769236.

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Human mucous proteinase inhibitor (MPI) is present in bronchial secretions, where it participates in the protection of lung structures against degradation by leukocyte elastase. The protein has been localized by immunohistochemical studies and immunogold labeling essentially in the serous cells of the submucosal glands and also in the surface epithelial cells of central and peripheral airways. However, until now no gene expression study has been performed at the tissue level. In this study, in situ hybridization was used to precisely study MPI mRNA expression in bronchial tissue sections with a specific radiolabeled oligonucleotide probe. By light microscopy, MPI gene expression was localized exclusively in the serous and seromucinous acini of the submucosal glands of large airways. The MPI gene was expressed in submucosal glands of normal and carcinomatous tissue sections, whereas it was not expressed in bronchial and bronchiolar surface epithelia.

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13

Inglis, S. K., M. R. Corboz, A. E. Taylor y S. T. Ballard. "In situ visualization of bronchial submucosal glands and their secretory response to acetylcholine". American Journal of Physiology-Lung Cellular and Molecular Physiology 272, n.º 2 (1 de febrero de 1997): L203—L210. http://dx.doi.org/10.1152/ajplung.1997.272.2.l203.

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Airway submucosal glands secrete both macromolecules and liquid, yet the mechanisms by which these substances are secreted are not well understood. In this study, a video microscope was used to directly visualize the submucosal glands in isolated porcine distal bronchi and to observe their responses to acetylcholine (ACh), a glandular secretagogue. Submucosal glands were classified as either "antral," "linear," or "convoluted" glands based on the morphology of their terminal collecting ducts. Because antral duct glands were most easily visualized, the response to ACh was studied in detail in this gland type. Within 5-10 s after addition of 10 microM ACh, the cross-sectional area of the gland duct openings to the airway surface increased severalfold but returned to pre-ACh dimensions within 1 min. Between 30 s and 10 min after ACh addition, spherical particles (1-10 microm) entered the antral ducts from distal acini and exited through the duct openings to the airway surface. Some of the particles were retained within the antral duct where they were kept in constant motion by the action of cilia present within the antral duct. The particles, which are likely to contain the macromolecular secretory products of mucous and/or serous cells, maintained their spherical shape within the gland duct, suggesting that the secretion product was membrane bound. To our knowledge, these studies provide the first description of airway submucosal gland secretion as viewed in situ.

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Hejal, R., K. P. Strohl, B. Erokwu, N. S. Cherniack y M. A. Haxhiu. "Pathways and mechanisms involved in neural control of laryngeal submucosal gland secretion". Journal of Applied Physiology 75, n.º 6 (1 de diciembre de 1993): 2347–52. http://dx.doi.org/10.1152/jappl.1993.75.6.2347.

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The purpose of this study was to define the pathways and mechanisms involved in the neural regulation of laryngeal mucosal gland functions. In anesthetized, paralyzed, and artificially ventilated dogs, the responses of laryngeal submucosal glands to stimulation of laryngeal mechanoreceptors and peripheral chemoreceptors were examined by measuring the number of hillocks and volume of secreted fluid before and after activation of sensory nerve endings. Compared with a control period, the number of hillocks and volume of secreted fluid significantly increased (P < 0.05) with mechanical stimulation of the vocal folds (n = 13) and with chemical activation of peripheral chemoreceptors by systemic administration of sodium cyanide (100 micrograms/kg; n = 11). The reflex responses induced by vocal fold stimulation and activation of peripheral chemoreceptors were slightly decreased by interrupting transmission in the recurrent laryngeal nerves (P > 0.05) and were abolished by subsequent sectioning of superior laryngeal nerves or prior intravenous administration of atropine methylnitrate (P < 0.05). In denervated animals, topical application of nicotine on laryngeal epithelium caused significant activation of submucosal glands (P < 0.05). We conclude that laryngeal secretion can be significantly altered reflexly by stimulation of laryngeal sensory nerve endings and peripheral chemoreceptors, that both superior and recurrent laryngeal nerves convey cholinergic outflow to laryngeal submucosal glands, and that nicotine acting locally activates laryngeal submucosal glands.

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Saitoh, Hiroki, Tohru Masuda, Sanae Shimura, Toshiaki Fushimi y Kunio Shirato. "Secretion and gene expression of secretory leukocyte protease inhibitor by human airway submucosal glands". American Journal of Physiology-Lung Cellular and Molecular Physiology 280, n.º 1 (1 de enero de 2001): L79—L87. http://dx.doi.org/10.1152/ajplung.2001.280.1.l79.

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Submucosal glands were isolated within 4 h of death from tracheae and bronchi obtained from autopsied lungs, and the secretory response of secretory leukocyte protease inhibitor (SLPI) was examined with ELISA and a secretory index. Although human neutrophil elastase (HNE) at low concentrations increased SLPI secretion above the control level (i.e., 149% of control level at 10−11 M), HNE at high concentrations significantly decreased it below the control level (i.e., 16% of control level at 10−7 M). The decrease in SLPI concentration was shown to result from the degradation of SLPI by excessive HNE. Methacholine induced significant secretion (i.e., 363% of control level at 10−5 M) that was abolished by both M1 and M3 receptor antagonists. A semiquantitative analysis of SLPI mRNA by RT-PCR and Southern blot showed that compared with the superficial epithelium, submucosal glands had a 30-fold or higher level of SLPI mRNA. Both HNE and methacholine significantly increased the level of SLPI mRNA in submucosal glands in a dose-dependent manner (i.e., 357% of control level at 10−7 M and 175% of control level at 10−5 M, respectively). These findings indicate that human airway submucosal glands can transcribe 30-fold or more SLPI mRNA than the superficial epithelium and that SLPI mRNA transcription and secretion are regulated by both HNE and muscarinic receptors.

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Engelhardt, J. F., H. Schlossberg, J. R. Yankaskas y L. Dudus. "Progenitor cells of the adult human airway involved in submucosal gland development". Development 121, n.º 7 (1 de julio de 1995): 2031–46. http://dx.doi.org/10.1242/dev.121.7.2031.

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A bronchial xenograft model of the human airway was used to identify submucosal gland progenitor cells within the surface airway epithelium. Lineage analysis using recombinant retroviruses has demonstrated considerable diversity in the cellular composition of expanded clones within reconstituted xenograft airway epithelium. These findings provide evidence for the existence of multiple progenitors in the airway with either limited or pluripotent capacity for differentiation. Furthermore, the development of transgene-expressing submucosal glands was associated with a single subset of surface airway epithelial clones. This gland progenitor cell demonstrated two discernible characteristics consistent with the identification of an airway stem cell including: (1) pluripotent capacity for airway differentiation and (2) a two-fold higher proliferative rate than other observed clone types. The number of progenitor cells involved in gland development was also assessed by clonal analysis using alkaline phosphatase and beta-galactosidase transgenes. These studies demonstrated that more than one airway progenitor cell is involved in the initial stages of gland development. A second explanation for the high prevalence of non-clonality in developing glands was suggested from three-dimensional reconstruction of transgene marked glands. These reconstruction experiments demonstrated that 27% of glands contained more than one duct to the surface airway epithelium. This observation suggests a novel mechanism of gland morphogenesis by which independently formed glands interact to join glandular lumens. Such a mechanism of glandular development and morphogenesis may play an important role in normal submucosal gland development and/or the progression of hypersecretory diseases of the adult human airway as seen in cystic fibrosis, chronic bronchitis and asthma. The identification of progenitor cells with the capacity to form submucosal glands has implications on the targets for gene therapy in cystic fibrosis.

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Ballard, S. T., J. D. Fountain, S. K. Inglis, M. R. Corboz y A. E. Taylor. "Chloride secretion across distal airway epithelium: relationship to submucosal gland distribution". American Journal of Physiology-Lung Cellular and Molecular Physiology 268, n.º 3 (1 de marzo de 1995): L526—L531. http://dx.doi.org/10.1152/ajplung.1995.268.3.l526.

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To evaluate the possible relationship between submucosal glands and transepithelial Cl- secretion, we compared the bioelectric properties of two distal airway regions: bronchioles, which contain few submucosal glands, and small bronchi, which contain numerous glands. Intact distal bronchi were dissected from the lungs of 4-8 wk old pigs and cannulated with micropipettes and perfused. Transepithelial potential difference (PD), short-circuit current (Isc), and barrier resistance (Rm) in distal bronchi, determined by cable analysis, were -3.0 +/- 0.4 mV, 50.7 +/- 5.9 microA/cm2, and 59.6 +/- 5.9 omega.cm2, respectively (means +/- SE). Bumetanide (10 microM), which blocks Cl- secretion through inhibition of Na(+)-K(+)-2Cl- cotransport, reduced Isc in distal bronchi by 30.0 +/- 5.5 microA/cm2 (59.0% of the total Isc). By comparison, a previous study of porcine distal airways [S.T. Ballard and A.E. Taylor, Am. J. Physiol. 267 (Lung Cell. Mol. Physiol. 11): L79-L84, 1994] determined that bumetamide-sensitive Isc in bronchioles was 2.6 +/- 1.4 microA/cm2 (only 9.0% of the total Isc). Submucosal gland duct openings to the luminal surface were identified microscopically and counted in representative fields. In eight bronchioles, 6.8 +/- 4.4 gland duct openings/cm2 of airway surface were observed, whereas seven distal bronchi contained 916.8 +/- 84.0 gland duct openings/cm2, over a 100-fold difference. These data suggest that a direct relationship may exist between the magnitude of active transepithelial Cl- secretion and the presence of submucosal glands in normal distal airways.

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Widdicombe, Jonathan H. "Early studies of airway submucosal glands". American Journal of Physiology-Lung Cellular and Molecular Physiology 316, n.º 6 (1 de junio de 2019): L990—L998. http://dx.doi.org/10.1152/ajplung.00068.2019.

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This historical article provides a comprehensive review of early research on the structure and function of airway submucosal glands. The literature before 1950 or so, is virtually unknown, but in addition to being of historical interest it contains much of relevance to current research. Airway glands were first mentioned in 1602. The first description of their general form, size, and distribution was in 1712. Gland morphology was determined in 1827 by injecting mercury into their openings. Wax was later used. Detailed comparative information for all regions of the tracheobronchial tree was provided by Frankenhauser in 1879 ( Untersuchungen uber den bau der Tracheo-Bronchial-Schleimhaut). Histological studies began in 1870, and by the end of the 19th century, all the major histological features had been described. The first physiological studies on airway mucous secretion were published in 1892. Kokin, in 1896 ( Archiv für die gesamte Physiologie des Menschen und der Tiere 63: 622–630), was the first to measure secretion from individual glands. It was not, however, until 1933 that gland secretion was quantified. This early literature raises important questions as to the role of the collecting duct epithelium in modifying primary secretions. It also provides perhaps the most accurate measure of basal gland secretion in vivo.

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Long, John D. y Roy C. Orlando. "Esophageal Submucosal Glands: Structure and Function". American Journal of Gastroenterology 94, n.º 10 (octubre de 1999): 2818–24. http://dx.doi.org/10.1111/j.1572-0241.1999.1422_b.x.

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Inglis, S. K. y S. M. Wilson. "Cystic fibrosis and airway submucosal glands". Pediatric Pulmonology 40, n.º 4 (2005): 279–84. http://dx.doi.org/10.1002/ppul.20183.

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Shimura, S., T. Sasaki, H. Sasaki y T. Takishima. "Contractility of isolated single submucosal gland from trachea". Journal of Applied Physiology 60, n.º 4 (1 de abril de 1986): 1237–47. http://dx.doi.org/10.1152/jappl.1986.60.4.1237.

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We isolated single submucosal glands from canine and feline trachea. Examination by light and electron microscope showed that these isolated glands consist mainly of glandular tissue, and no smooth muscle. Cell components in the glandular tissue were ultrastructurally normal, and myoepithelial cells surrounded acini and secretory tubules. In response to methacholine, the mucus was squeezed from the tip of the collecting ducts in coincidence with the contraction of the glands. The contractile properties of isolated single glands were examined with a force transducer. Cholinergic agents (methacholine and acetylcholine) as well as 40–150 mM K+ showed a dose-response relationship and induced tension up to 12 mg. The length-tension relationship was also observed. The removal of Ca2+ from the medium eliminated contractile response. Caffeine induced approximately 30% of the response to methacholine, and phenylephrine, a tension less than 30% of that with methacholine. These findings suggest that squeezing of mucus due to the contraction of myoepithelial cells has an important effect on secretory response of airway submucosal glands.

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Bingle, Lynne y Colin D. Bingle. "Distribution of human PLUNC/BPI fold-containing (BPIF) proteins". Biochemical Society Transactions 39, n.º 4 (20 de julio de 2011): 1023–27. http://dx.doi.org/10.1042/bst0391023.

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Although gene expression studies have shown that human PLUNC (palate, lung and nasal epithelium clone) proteins are predominantly expressed in the upper airways, nose and mouth, and proteomic studies have indicated they are secreted into airway and nasal lining fluids and saliva, there is currently little information concerning the localization of human PLUNC proteins. Our studies have focused on the localization of three members of this protein family, namely SPLUNC1 (short PLUNC1), SPLUNC2 and LPLUNC1 (long PLUNC1). Western blotting has indicated that PLUNC proteins are highly glycosylated, whereas immunohistochemical analysis demonstrated distinct patterns of expression. For example, SPLUNC2 is expressed in serous cells of the major salivary glands and in minor mucosal glands, whereas SPLUNC1 is expressed in the mucous cells of these glands. LPLUNC1 is a product of a population of goblet cells in the airway epithelium and nasal passages and expressed in airway submucosal glands and minor glands of the oral and nasal cavities. SPLUNC1 is also found in the epithelium of the upper airways and nasal passages and in airway submucosal glands, but is not co-expressed with LPLUNC1. We suggest that this differential expression may be reflected in the function of individual PLUNC proteins.

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23

Sakurai, Toshiyuki, Junichi Akiyama, Hideki Utagawa, Takeichi Yoshida, Naoki Akazawa, Yuko Nagaoki, Takao Oshima et al. "A submucosal heterotopia of gastric glands removed by endoscopic submucosal dissection". Progress of Digestive Endoscopy 72, n.º 2 (2008): 72–73. http://dx.doi.org/10.11641/pde.72.2_72.

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24

Shintaku, Masayuki, Makoto Ohta, Akito Noguchi y Masako Shintaku. "Esophageal Intramural Pseudodiverticulosis: A Histopathological and Immunohistochemical Study of 2 Cases". Case Reports in Gastroenterology 16, n.º 1 (28 de abril de 2022): 270–77. http://dx.doi.org/10.1159/000524496.

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Esophageal intramural pseudodiverticulosis (EIPD) is a rare disorder characterized by an abnormal, cyst-like dilatation of the excretory ducts of esophageal submucosal glands. We aimed to elucidate the histopathological features and immunohistochemical properties of the epithelial lining of the cyst-like lesions in EIPD. We performed a histopathological and immunohistochemical study of 2 cases (one autopsy and one surgical) of EIPD. The ductal walls consisted of inner ductal cells, which were cytokeratin (CK) 7-positive and CK5/6-negative, and outer basal cells, which were CK7-negative and CK5/6-positive. The ductal epithelium frequently showed squamous metaplasia and rarely simulated a false diverticulum. Immunohistochemistry for CK7 was useful for distinction between the conditions because the surface epithelium was negative for CK7. We also confirmed that myoepithelial cells in the acinar portion of submucosal glands were well-preserved in EIPD, the finding that explained the periodic opening and closing movements of orifices of cyst-like lesions in this disorder. The immunohistochemical properties of the epithelial lining of cyst-like lesions in EIPD were essentially similar to those of the normal ducts of submucosal glands.

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25

HOVENBERG, Hans W., Julia R. DAVIES y Ingemar CARLSTEDT. "Different mucins are produced by the surface epithelium and the submucosa in human trachea: identification of MUC5AC as a major mucin from the goblet cells". Biochemical Journal 318, n.º 1 (15 de agosto de 1996): 319–24. http://dx.doi.org/10.1042/bj3180319.

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Mucins were extracted from the epithelial surface and the submucosal tissue of human trachea in order to enrich glycoproteins from the goblet cells and the submucosal glands respectively. The macromolecules were purified using density-gradient centrifugation, and the presence of the MUC5AC mucin was investigated using an antiserum raised against a synthetic peptide based on the sequence of the MUC5AC apoprotein. Mucins from the surface epithelium showed a higher reactivity with the antiserum relative to carbohydrate than those from the submucosa, and ion-exchange HPLC of reduced subunits revealed the presence of two distinct mucin populations in the samples. The predominant species from the surface epithelium was more acidic than the major population from the submucosa and showed a strong reactivity with the anti-MUC5AC antiserum. In contrast, the major portion of the submucosal mucins were less acidic and showed no MUC5AC reactivity, although a more acidic population did react with the antibody. Rate-zonal centrifugation showed that the MUC5AC mucin from the surface epithelium is smaller than the major submucosal mucin, and that both are composed of subunits. Immunolocalization confirmed that the MUC5AC mucin from human trachea originates from the goblet cells and that this glycoprotein is not a major product of the submucosal glands.

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26

Rha, Ki Sang, Yukihiko Yasui, Yuichi Majima, Katsuma Nakano, Yasuo Sakakura y Akinori Ishihara. "Distribution of Substance P Immunoreactive Nerve Fibers in the Tracheal Submucosal Gland of Cats". Annals of Otology, Rhinology & Laryngology 103, n.º 3 (marzo de 1994): 222–26. http://dx.doi.org/10.1177/000348949410300310.

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Immunohistochemistry combined with electron microscopy was employed to investigate the distribution of substance P—immunoreactive (SP-IR) nerve fibers in the tracheal submucosal gland of cats. The SP-IR nerve fibers were found to form a network around the glands. Numerous varicosities were also detected within the basement membrane of the acini and secretory tubules. All the intraglandular varicosities showed close spatial contact with serous cells, mucous cells, and myoepithelial cells. Our findings suggest that substance P—induced mucus secretion from tracheal submucosal glands in cats may be caused not only by a glandular contractile response of myoepithelial cells, but also by direct stimulation to both serous and mucous cells.

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27

Cho, Hyung-Ju, Nam Soo Joo y Jeffrey J. Wine. "Mucus secretion from individual submucosal glands of the ferret trachea". American Journal of Physiology-Lung Cellular and Molecular Physiology 299, n.º 1 (julio de 2010): L124—L136. http://dx.doi.org/10.1152/ajplung.00049.2010.

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Mucus secretion from individual tracheal glands in adult ferrets was studied with time-lapse optical imaging of mucus droplets under an oil layer. Density of functional glands (determined by responses to 1 μM carbachol) was 1.5 ± 0.3 per mm2 ( n = 6). Secretion rates (in pl·min−1·gland−1) were as follows: 4.1 ± 0.7 basal (unstimulated; n = 27, 669 glands), 338 ± 70 to 10 μM forskolin ( n = 8, 90 glands), 234 ± 13 to 1 μM VIP ( n = 6, 57 glands), 183 ± 92 to 10 μM isoproterenol ( n = 3, 33 glands), 978 ± 145 to 1 μM carbachol ( n = 11, 131 glands), and 1,348 ± 325 to 10 μM phenylephrine ( n = 7, 74 glands). The potency (EC50, in μM) and efficacy ( Vmax, in pl·min−1·gland−1) were 7.6 (EC50) and 338 ± 16 ( Vmax) to forskolin, 1.0 (EC50) and 479 ± 19 ( Vmax) to VIP, 0.6 (EC50) and 1,817 ± 268 ( Vmax) to carbachol, and 3.7 (EC50) and 1,801 ± 95 ( Vmax) to phenylephrine. Although carbachol and phenylephrine were equally effective secretagogues, only carbachol caused contractions of the trachealis muscle. Synergy was demonstrated between 300 nM isoproterenol and 100 nM carbachol, which, when combined, produced a secretion rate almost fourfold greater than predicted from their additive effect. The dependence of fluid secretion on Cl− and HCO3− varied depending on the mode of stimulation. Secretion stimulated by VIP or forskolin was reduced by ∼60% by blocking either anion, while carbachol-stimulated secretion was blocked 68% by bumetanide and only 32% by HEPES replacement of HCO3−. These results provide parametric data for comparison with fluid secretion from glands in ferrets lacking CFTR.

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28

Garman, Katherine S. "Origin of Barrett’s Epithelium: Esophageal Submucosal Glands". Cellular and Molecular Gastroenterology and Hepatology 4, n.º 1 (julio de 2017): 153–56. http://dx.doi.org/10.1016/j.jcmgh.2017.01.016.

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29

Abdulnour-Nakhoul, Solange, Nazih L. Nakhoul, Scott A. Wheeler, Paul Wang, Eric R. Swenson y Roy C. Orlando. "HCO3−secretion in the esophageal submucosal glands". American Journal of Physiology-Gastrointestinal and Liver Physiology 288, n.º 4 (abril de 2005): G736—G744. http://dx.doi.org/10.1152/ajpgi.00055.2004.

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The mammalian esophagus has the capacity to secrete a HCO3−and mucin-rich fluid in the esophageal lumen. These secretions originate from the submucosal glands (SMG) and can contribute to esophageal protection against refluxed gastric acid. The cellular mechanisms by which glandular cells achieve these secretions are largely unknown. To study this phenomenon, we used the pH-stat technique to measure luminal alkali secretion in an isolated, perfused pig esophagus preparation. Immunohistochemistry was used to localize receptors and transporters involved in HCO3−transport. The SMG-bearing esophagus was found to have significant basal alkali secretion, predominantly HCO3−, which averaged 0.21 ± 0.04 μeq·h−1·cm−2. This basal secretion was doubled when stimulated by carbachol but abolished by HCO3−or Cl−removal. Basal- and carbachol-stimulated secretions were also blocked by serosal application of atropine, pirenzipine, DIDS, methazolamide, and ethoxzolamide. The membrane-impermeable carbonic anhydrase inhibitor benzolamide, applied to the serosal bath, partially inhibited basal HCO3−secretion and blocked the stimulation by carbachol. Immunohistochemistry using antibodies to M1cholinergic receptor or carbonic anhydrase-II enzyme showed intense labeling of duct cells and serous demilunes but no labeling of mucous cells. Labeling with an antibody to Na+-(HCO3−)n(rat kidney NBC) was positive in ducts and serous cells, whereas labeling for Cl−/HCO3−exchanger (AE2) was positive in duct cells but less pronounced in serous cells. These data indicate that duct cells and serous demilunes of SMG play a role in HCO3−secretion, a process that involves M1cholinergic receptor stimulation. HCO3−transport in these cells is dependent on cytosolic and serosal membrane-bound carbonic anhydrase. HCO3−secretion is also dependent on serosal Cl−and is mediated by DIDS-sensitive transporters, possibly NBC and AE2.

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30

Ballard, Stephen T. y Sarah K. Inglis. "Liquid secretion properties of airway submucosal glands". Journal of Physiology 556, n.º 1 (30 de marzo de 2004): 1–10. http://dx.doi.org/10.1113/jphysiol.2003.052779.

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31

AbdullGaffar, Badr y Hoda Quraishi. "Histopathologic Manifestations of Crohn Disease in Duodenal Endoscopy Biopsy: The Value of Different Patterns of Involvement of Brunner Glands". International Journal of Surgical Pathology 29, n.º 7 (26 de febrero de 2021): 710–15. http://dx.doi.org/10.1177/1066896921998438.

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Crohn disease (CD) not uncommonly involves the upper gastrointestinal tract, usually gastric antrum and proximal duodenum. The most consistent histopathologic manifestations of CD in duodenal biopsies are mucosal erosion, focal active inflammation, and granulomas. Since CD is a transmural inflammation and since duodenal biopsy may include submucosal Brunner glands, we aimed to find if CD has any specific histopathologic manifestations in Brunner gland lobules and their ducts compared to other duodenal inflammatory lesions. We carried out a retrospective review study over 6 years retrieving duodenal biopsy specimens in CD patients. We compared duodenal specimens involved by CD with other inflammatory lesions, for example, ulcerative colitis (UC), Helicobacter pylori-associated gastritis, non-Helicobacter gastritis, Celiac sprue, infections, and drugs. We found focal active duodenitis and erosion in CD cases and non-CD cases. Granulomas were found in CD cases. Five cases of CD showed inflammatory and degenerative changes of Brunner glands. Focal patchy active inflammation of only portion of submucosal Brunner gland lobule, mucosal Brunner glands, and their ducts was solely found in CD cases. This focally enhanced inflammation of Brunner glands was not found in other lesions. Whether this phenomenon of focal active “lobulitis” and “ductitis” is a specific sign of duodenal CD compared to UC and other inflammatory lesions warrants verification. We encourage endoscopists to include submucosal Brunner lobules in their duodenal biopsy samples and pathologists to look for these patterns of involvement particularly in patients suspected of CD.

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32

Luan, Xiaojie, Julian S. Tam, Santosh Jagadeeshan, Nikolay Grishchenko, Noman Hassan, Paula Gioino, Alan M. Shipley, Terry E. Machen y Juan P. Ianowski. "Airway submucosal glands from cystic fibrosis swine suffer from abnormal ion transport across the serous acini, collecting duct, and ciliated duct". American Journal of Physiology-Lung Cellular and Molecular Physiology 318, n.º 5 (1 de mayo de 2020): L931—L942. http://dx.doi.org/10.1152/ajplung.00219.2019.

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The human airway is protected by an efficient innate defense mechanism that requires healthy secretion of airway surface liquid (ASL) to clear pathogens from the lungs. Most of the ASL in the upper airway is secreted by submucosal glands. In cystic fibrosis (CF), the function of airway submucosal glands is abnormal, and these abnormalities are attributed to anomalies in ion transport across the epithelia lining the different sections of the glands that function coordinately to produce the ASL. However, the ion transport properties of most of the anatomical regions of the gland have never been measured, and there is controversy regarding which segments express CFTR. This makes it difficult to determine the glandular abnormalities that may contribute to CF lung disease. Using a noninvasive, extracellular self-referencing ion-selective electrode technique, we characterized ion transport properties in all four segments of submucosal glands from wild-type and CFTR−/− swine. In wild-type airways, the serous acini, mucus tubules, and collecting ducts secrete Cl− and Na+ into the lumen in response to carbachol and forskolin stimulation. The ciliated duct also transports Cl− and Na+ but in the opposite direction, i.e., reabsorption from the ASL, which may contribute to lowering Na+ and Cl− activities in the secreted fluid. In CFTR−/− airways, the serous acini, collecting ducts, and ciliated ducts fail to transport ions after forskolin stimulation, resulting in the production of smaller volumes of ASL with normal Cl−, Na+, and K+ concentration.

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33

Shimura, S., T. Sasaki, H. Okayama, H. Sasaki y T. Takishima. "Effect of substance P on mucus secretion of isolated submucosal gland from feline trachea". Journal of Applied Physiology 63, n.º 2 (1 de agosto de 1987): 646–53. http://dx.doi.org/10.1152/jappl.1987.63.2.646.

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To elucidate how substance P (SP) produces submucosal gland secretion, we examined the effects of SP on the glandular contractile response and 3H-labeled glycoconjugate release in isolated submucosal glands from feline tracheae. SP (10(-12) to 10(-4) M) produced dose-dependent increases in the contractile response, and the maximal tension induced by SP was approximately 70% of the response to methacholine. SP-induced contraction is blocked completely by atropine and augmented by neostigmine. Pretreatment with hemicholinium 3, an acetylcholine synthesis inhibitor, inhibited the contractile response to SP. Pretreatment with tetrodotoxin did not inhibit the contractile response to SP. Capsaicin induced tension of a magnitude similar to that of SP. SP (10(-7) M) produced a significant increase (74% above control) in radiolabeled glycoconjugate release from isolated glands, whereas SP had no significant effects on glycoconjugate release from tracheal explants, probably because of epithelial suppression. Atropine abolished SP-evoked glycoconjugate release in isolated glands. Our findings indicate that 1) SP induces glandular contraction, which is related to the squeezing of mucus in the ducts and secretory tubules, 2) SP stimulates radiolabeled glycoconjugate release in isolated submucosal gland, probably involving mucus synthesis and/or cellular secretion, and 3) these two actions are mediated by a peripheral cholinergic mechanism.

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34

Yang, C. M., J. M. Farley y T. M. Dwyer. "Muscarinic stimulation of submucosal glands in swine trachea". Journal of Applied Physiology 64, n.º 1 (1 de enero de 1988): 200–209. http://dx.doi.org/10.1152/jappl.1988.64.1.200.

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The properties of muscarinic acetylcholine receptors (mAChR) on tracheal explants and isolated submucosal gland cells were determined using [3H]quinuclidinyl benzilate ([3H]QNB) and N-[3H]methylscopolamine ([3H]NMS) as ligands. Analysis of competitive displacement of ([3H]NMS binding by pirenzepine demonstrated the presence of M1- (27 +/- 2%) and M2G- (73 +/- 2%) receptors on isolated tracheal submucosal gland cells (TSGC's) in control. Daily administration of diisopropylfluorophosphate (DFP) inhibited cholinesterase activity by greater than 95%. After 7 days of DFP treatment, [3H]QNB binding to intact TSGC's decreased from 14.2 +/- 0.6 to 6.3 +/- 0.8 fmol/10(6) cells; similarly, [3H]NMS binding fell from 8.1 +/- 1.9 to 2.0 +/- 0.8 fmol/10(6) cells. The loss of mAChR's was predominantly of the M2G subtype with the relative proportion dropping to 33%. In addition, 90% of the receptors assumed the high-affinity state for carbachol displacement of [3H]NMS. Mucus secretion was quantitated by measuring the release of 3H-labeled mucus macromolecules from explants of tracheal submucosal glands and isolated cells. Acetylcholine (ACh), 2 X 10(-5) M, stimulated mucus secretion by 2.5 and 2.3 times the basal rate, respectively. Elimination of acetylcholinesterase (AChe) by DFP increased the ACh sensitivity by 18- and 5-fold. Tracheal explants or TSGC's obtained 2 h after an in vivo DFP treatment showed a 6- and 3-fold ACh stimulation. This ACh sensitivity decreased during the continued daily dosing with DFP such that only a 1.3- and 1.1-fold ACh stimulation was apparent after 7 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

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35

Sasaki, T., S. Shimura, K. Ikeda, H. Sasaki y T. Takishima. "Sodium efflux from isolated submucosal gland in feline trachea". American Journal of Physiology-Lung Cellular and Molecular Physiology 258, n.º 2 (1 de febrero de 1990): L112—L117. http://dx.doi.org/10.1152/ajplung.1990.258.2.l112.

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We examined Na efflux, as an indicator of electrolyte (or water) secretion from isolated feline tracheal submucosal glands. After incubation with 22NaCl-containing KRB solution (pH 7.4) at 37 degrees C, the 22Na-loaded glands were transferred to a superfusion apparatus in which perfusate was continuously pumped to the glands at a flow rate of 2.5 ml/min and sampled at 18-s intervals for 10-15 min. After 5 min of perfusion, a pharmacological or electrical field stimulation (FS) was given to the isolated glands. The instantaneous rate constant was calculated by measuring the radioactivity (counts/min) of each effluent sample. The mean rate constant of the base-line 22Na efflux was 0.21 min-1, which fell significantly to 0.03 min-1 after treatment with ouabain. Both methacholine and phenylephrine significantly accelerated the 22Na efflux to 3.6-fold and 1.8 times base-line efflux, respectively. FS produced a significant increase in the rate constant, and the increase was abolished by pretreatment with ouabain or tetrodotoxin. Further, atropine or phentolamine significantly suppressed the FS-evoked increase in the rate constant to 76 and 84%, respectively, of the maximal response evoked by FS alone. These results indicate that Na efflux from feline tracheal submucosal glands, which is dependent on ouabain-sensitive Na-K-ATPase activity in the secretory cells, is stimulated by both cholinergic and alpha-adrenergic agonists.

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36

Jacquot, J., E. Puchelle, J. Hinnrasky, C. Fuchey, C. Bettinger, C. Spilmont, N. Bonnet et al. "Localization of the cystic fibrosis transmembrane conductance regulator in airway secretory glands". European Respiratory Journal 6, n.º 2 (1 de febrero de 1993): 169–76. http://dx.doi.org/10.1183/09031936.93.06020169.

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Cystic fibrosis (CF) is caused by mutations in the gene coding for the CF transmembrane conductance regulator (CFTR). From human normal tracheal submucosal gland cells in culture, we identified endogenous CFTR as a 170 kDa protein, consistent with that of fully glycosylated, mature CFTR molecule. This observation led to the hypothesis that airway secretory glands could be an important site for the CFTR expression. Using anti-human CFTR polyclonal and monoclonal antibodies, we examined the cellular and subcellular localization of the CFTR protein in airway submucosal glands from human and bovine tracheal tissues as well as in tracheal gland cell cultures. In human tracheal tissue, CFTR immunolabelling was present along both the apical and basolateral plasma membranes of glandular mucous cells. In contrast, CFTR was associated with the secretory granules of glandular serous cells. Using immunogold electron microscopy, we demonstrated that CFTR protein was more specifically associated with the membrane of serous cell secretory granules. In bovine tracheal tissue CFTR labelling was also identified in the secretory granules of glandular serous cells. In contrast, when bovine and human tracheal gland cells were cultured, no mature secretory granules were present, but a predominantly intracytoplasmic distribution of CFTR was observed. Our data thus suggest that in airway tissues, CFTR could be involved in intracellular processes of the mucus exocytosis in submucosal secretory glands.

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37

Shimura, S., T. Sasaki, H. Okayama, H. Sasaki y T. Takishima. "Neural control of contraction in isolated submucosal gland from feline trachea". Journal of Applied Physiology 62, n.º 6 (1 de junio de 1987): 2404–9. http://dx.doi.org/10.1152/jappl.1987.62.6.2404.

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To determine the autonomic innervation to myoepithelial cells of submucosal gland, we applied electrical field stimulation (FS) to the intrinsic nerves in isolated submucosal glands from feline tracheae. FS induced contraction that was voltage or frequency dependent and abolished by pretreatment with tetrodotoxin. DMPP (1,1-dimethyl-4-phenylpiperazinium iodide) did not produce any significant contraction, and pretreatment with hexamethonium did not alter the response to FS. Atropine inhibited the contractile response to FS and neostigmine augmented the response to FS. Serotonin also augmented the response to FS, whereas the response to methacholine remained unchanged in the presence of serotonin. Phentolamine reduced the response to FS by 15% of control, whereas propranolol induced no significant changes in the response to FS. No significant inhibitory responses were observed by FS. Our findings indicate that the contraction of tracheal submucosal glands is mediated mainly by cholinergic nerves via muscarinic receptors and in small part by adrenergic nerves via alpha-receptors, and serotonin potentiates the contractile response to FS at the postganglionic nerve.

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38

Schultz, H. D., A. M. Roberts, C. Bratcher, H. M. Coleridge, J. C. Coleridge y B. Davis. "Pulmonary C-fibers reflexly increase secretion by tracheal submucosal glands in dogs". Journal of Applied Physiology 58, n.º 3 (1 de marzo de 1985): 907–10. http://dx.doi.org/10.1152/jappl.1985.58.3.907.

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Stimulation of bronchial C-fibers evokes a reflex increase in secretion by tracheal submucosal glands, but the influence of pulmonary C-fibers on tracheal gland secretion is uncertain. In anesthetized dogs with open chests, we sprayed powdered tantalum on the exposed mucosa of a segment of the upper trachea to measure the rate of secretion by submucosal glands. Secretions from the gland ducts caused elevations (hillocks) in the tantalum layer. We counted hillocks at 10-s intervals for 60 s before and 60 s after we injected capsaicin (10–20 micrograms/kg) into the right atrium to stimulate pulmonary C-fiber endings. Right atrial injection of capsaicin increased the rate of hillock formation fourfold, but left atrial injection had no significant effect. The response was abolished by cutting the vagus nerves or cooling them to 0 degree C. We conclude that the reflex increase in tracheal submucosal gland secretion evoked by right atrial injection of capsaicin was initiated as capsaicin passed through the pulmonary vascular bed, and hence that pulmonary C-fibers, like bronchial C-fibers, reflexly increase airway secretion.

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39

Satoh, M., S. Shimura, H. Ishihara, K. Yamada, T. Masuda, T. Sasaki, H. Sasaki y T. Takishima. "Dexamethasone modulation of ion transport and fluid movement across airway epithelium". American Journal of Physiology-Lung Cellular and Molecular Physiology 264, n.º 4 (1 de abril de 1993): L376—L381. http://dx.doi.org/10.1152/ajplung.1993.264.4.l376.

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Electrolyte or fluid is secreted across airway mucosa by both superficial epithelium and submucosal glands. To understand the effect of glucocorticoid on fluid movement across airway mucosa, we examined the effects of dexamethasone (Dex) on bioelectric properties of canine and feline tracheal epithelium and on 22Na efflux from isolated feline tracheal submucosal glands. Potential difference (PD) and short-circuit current (SCC) across tracheal epithelium were measured using an Ussing chamber, and conductance (G) was calculated as the ratio SCC/PD. Isolated glands were loaded with 22Na, and the rate constant (RC) of Na2+ efflux was calculated by measuring the radioactivity of each effluent sample. After treatment with 10(-9) to 10(-5) M Dex for up to 6 h, the epithelium and isolated glands were stimulated with isoproterenol (ISP) and methacholine (MCh), respectively. Dex treatment did not alter significantly baseline values of PD, SCC, or RC. However, Dex treatment produced a dose-dependent attenuation of ISP-evoked epithelial PD and SCC and of MCh-evoked glandular RC. In canine epithelium, pretreatment with 10(-5) M Dex for 6 h reduced by 40% the ISP (10(-6) M)-evoked rise in PD and SCC, whereas G remained unchanged. After 10(-5) M Dex treatment for 6 h, MCh (10(-5) M)-evoked RC in isolated glands was significantly less than in control glands (MCh alone) by 23%. These findings suggest that glucocorticoid decreases the fluid secretion across the airway mucosa, especially when the mucosa are stimulated.

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40

Shimura, S., H. Ishihara, M. Satoh, T. Masuda, N. Nagaki, H. Sasaki y T. Takishima. "Endothelin regulation of mucus glycoprotein secretion from feline tracheal submucosal glands". American Journal of Physiology-Lung Cellular and Molecular Physiology 262, n.º 2 (1 de febrero de 1992): L208—L213. http://dx.doi.org/10.1152/ajplung.1992.262.2.l208.

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We examined the effects of endothelin on both the trichloroacetic acid precipitable 3H-labeled glycoconjugate release and intracellular Ca2+ concentration ([Ca2+]i]) measured by the usage of fura-2 in submucosal glands isolated from feline trachea. Endothelin-1 produced a significant increase in glycoconjugate release from the isolated glands in a dose-dependent fashion, reaching a response of 161% of the control at 10(-6) M. Atropine, propranolol, phentolamine, or indomethacin did not produce any significant alterations in the ET-1-evoked glycoconjugate secretion from the isolated glands. In contrast, in tracheal explants which contained epithelium, ET-1 produced a significant reduction in the glycoconjugate secretion in a dose-dependent fashion, reaching a response of 59% of the control at 10(-6) M. In the presence of cultured epithelial cells, ET-1 also produced a significant reduction in the glycoconjugate secretion from isolated glands. In isolated glands, ET-1 produced a sustained increase in the [Ca2+]i which was abolished by the removal of Ca2+ from the medium or by the presence of cultured epithelial cells. Pretreatment with indomethacin failed to alter the epithelial inhibitory action evoked by ET-1 in both the glycoconjugate secretion and the [Ca2+]i in isolated glands. ET-2 and ET-3 failed to produce significant alterations in the glycoconjugate secretion or [Ca2+]i. These findings indicate 1) that ET-1 induces mucus glycoprotein secretion via a Ca2+ influx and 2) that it possibly augments the an epithelial action inhibitory to the mucus glycoprotein secretion from airway submucosal glands.

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41

Joo, Nam Soo, Jin V. Wu, Mauri E. Krouse, Yamil Saenz y Jeffrey J. Wine. "Optical method for quantifying rates of mucus secretion from single submucosal glands". American Journal of Physiology-Lung Cellular and Molecular Physiology 281, n.º 2 (1 de agosto de 2001): L458—L468. http://dx.doi.org/10.1152/ajplung.2001.281.2.l458.

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We describe an optical method to quantify single- gland secretion. Isolated tracheal mucosa were mounted at the air-Krebs interface and coated with oil. Gland secretions formed spherical bubbles that were digitally imaged at intervals, allowing rates of secretion to be calculated. We monitored 340 glands in 54 experiments with 12 sheep. Glands secreted basally at low rates (0.57 ± 0.04 nl · min−1 · gland−1, 123 glands) in tissues up to 9 h postharvest and at lower rates for up to 3 days. Carbachol (10 μM) stimulated secretion with an early transient and a sustained or oscillating phase. Peak secretion was 15.7 ± 1.2 nl · min−1 · gland−1 (60 glands); sustained secretion was 4.5 ± 0.5 nl · min−1 · gland−1 (10 glands). Isoproterenol and phenylephrine (10 μM each) stimulated only small, transient responses. We confirmed that cats have a large secretory response to phenylephrine (11.6 ± 3.7 nl · min−1 · gland−1, 12 glands), but pigs, sheep, and humans all have small responses (<2 nl · min−1 · gland−1). Carbachol-stimulated peak secretion was inhibited 56% by bumetanide, 67% by HCO[Formula: see text] replacement with HEPES, and 92% by both. The distribution of secretion rates was nonnormal, suggesting the existence of subpopulations of glands.

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42

Ichikawa, S., S. P. Sreedharan, R. L. Owen y E. J. Goetzl. "Immunochemical localization of type I VIP receptor and NK-1-type substance P receptor in rat lung". American Journal of Physiology-Lung Cellular and Molecular Physiology 268, n.º 4 (1 de abril de 1995): L584—L588. http://dx.doi.org/10.1152/ajplung.1995.268.4.l584.

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Peptidergic nerves in the respiratory tract release vasoactive intestinal peptide (VIP) and substance P (SP), which mediate physiological and immune functions. Antipeptide antibodies to type I VIP receptor (VIPR) and NK-1-type SP receptor (SPR) were used to identify these receptors in normal rat lungs. VIPRs and SPRs were detected on airway epithelium from the trachea to the respiratory bronchioles but not in alveoli, submucosal glands, or pulmonary smooth muscle, except for that of some pulmonary veins. VIPRs also were expressed on macrophages around capillaries, in tracheal and bronchial connective tissue, in alveolar walls, and in the subintima of pulmonary veins and some arterioles. The absence of receptors from airway smooth muscle and submucosal glands implies that mediation of some known effects of SP and VIP may be epithelial or macrophage dependent. Other types of VIPRs and SPRs on airway glands and smooth muscle may transduce direct effects. The similar localization of VIPRs and SPRs in rat lung suggests that VIP and SP may coordinately regulate some pulmonary functions.

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43

Melgarejo-Moreno, Pablo J., Inmaculada Ribera-Cortada y Diego Hellin-Meseguer. "Submucosal glands after maxillary sinus surgery. An experimental study in rabbits". Journal of Laryngology & Otology 110, n.º 7 (julio de 1996): 644–48. http://dx.doi.org/10.1017/s0022215100134504.

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AbstractThirty New Zealand White rabbits underwent unilateral partial or complete removal of maxillary sinus mucosa in order to evaluate submucosal maxillary sinus glands. After three months, specimens were taken for examination from all operated on and control sinuses. Bacteriological cultures, light and electron microscopy were performed. Histopathological findings showed a decrease in the number of serous glands and significant inflammation was present in the sinus in which there was complete surgical removal. Electron microscopy revealed changes in the secretory cells of the serous glands in the regenerated postsurgical mucosa.

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44

Joo, Nam Soo, Yamil Saenz, Mauri E. Krouse y Jeffrey J. Wine. "Mucus Secretion from Single Submucosal Glands of Pig". Journal of Biological Chemistry 277, n.º 31 (13 de mayo de 2002): 28167–75. http://dx.doi.org/10.1074/jbc.m202712200.

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45

Hashimoto, Rintaro, Hidetaka Hamamoto, Yuko Omori y Tokuma Tanuma. "Early gastric cancer on submucosal heterotopic gastric glands". Gastrointestinal Endoscopy 85, n.º 4 (abril de 2017): 851–52. http://dx.doi.org/10.1016/j.gie.2016.05.002.

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46

St. George, Judith A., Susan J. Nishio, Diane L. Cranz y Charles G. Plopper. "Carbohydrate cytochemistry of rhesus monkey tracheal submucosal glands". Anatomical Record 216, n.º 1 (septiembre de 1986): 60–67. http://dx.doi.org/10.1002/ar.1092160111.

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47

Berger, Gilead. "Eustachian tube submucosal glands in normal and pathological temporal bones". Journal of Laryngology & Otology 107, n.º 12 (diciembre de 1993): 1099–105. http://dx.doi.org/10.1017/s002221510012540x.

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Histological data concerning the structure and the topographical distribution of the eustachian tube submucosal glands is presented in 94 serially-sectioned temporal bones with and without otitis media. The vast majority of the tubal glands are located adjacent to the nasopharynx in the pharyngeal and midportion regions. Mixed glands which contain equal amounts of mucoid and serous elements are found in all age groups, in most specimens, either with or without otitis media. Furthermore, the glandular tissue, along these two medial regions of the tube, does not disclose significant quantitative differences between normal and inflamed specimens. Temporal bones without otitis media harbour few glands in the lateral four regions of the tube, while those with otitis media show a moderate increase of gland formation which is more noticeable in the pretympanum than in the regions around the isthmus (pre-isthmus, isthmus and post-isthmus regions). It is apparent that chronic inflammatory conditions like simple chronic otitis media and secretory otitis media are more often accompanied by gland formation, along the lateral four regions of the tube than acute otitis media.

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48

Hou, Jun-zhen, Ning-ning Dong, Bing Yue, Fan-dong Meng y Yong-jun Wang. "Autoimmune gastritis with a gastric hamartomatous inverted polyp and two hyperplastic polyps: a case report". Journal of International Medical Research 51, n.º 3 (marzo de 2023): 030006052311624. http://dx.doi.org/10.1177/03000605231162451.

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We report an unusual case of autoimmune gastritis (AIG) complicated with a submucosal tumor (SMT) and two pedunculated polyps in a 60-year-old man. The patient was admitted for epigastric distention, heartburn, and anorexia. Endoscopy showed an SMT in the fundus, two pedunculated polyps in the body, and markedly atrophic mucosa of the body and fundus. The SMT, measuring 20 mm in diameter, was resected by endoscopic submucosal dissection and histologically diagnosed as a gastric hamartomatous inverted polyp (GHIP), which is characterized by submucosal glandular proliferation, cystic dilatation, and calcification. The gland structures consisted of foveolar cells and pseudopyloric or mucous-neck cell types. The two pedunculated polyps that were resected by endoscopic mucosal resection were histologically diagnosed as hyperplastic polyps, which are characterized by hyperplastic foveolar glands with pseudopyloric or mucous-neck glands in the inflamed stroma in the mucosa, which consisted of almost the same types of lining cells as the GHIP in the fundus. Findings may indicate the relationship between GHIP, hyperplastic polyp, and AIG. We highlight considering GHIP as a differential diagnosis for an SMT in patients with AIG.

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49

Abdulnour-Nakhoul, Solange, Nazih L. Nakhoul y Roy C. Orlando. "Lumen-to-surface pH gradients in opossum and rabbit esophagi: role of submucosal glands". American Journal of Physiology-Gastrointestinal and Liver Physiology 278, n.º 1 (1 de enero de 2000): G113—G120. http://dx.doi.org/10.1152/ajpgi.2000.278.1.g113.

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The opossum esophagus, like that of humans, contains a network of submucosal glands with the capacity to secrete bicarbonate ions into the esophageal lumen. To evaluate the role of these glands in protecting the epithelial surface from acid insult, we measured the lumen-to-surface pH gradient in opossum esophagus at different luminal pH and compared it to that of rabbit esophagus, an organ devoid of submucosal glands. Sections of opossum and rabbit esophageal epithelium were mounted luminal side up in a modified Ussing chamber. pH-sensitive microelectrodes, positioned within 5 μm of the epithelial cell surface, were used to monitor surface pH during perfusion with solutions of different pH. At luminal pH 7.5, the pHsof both opossum and rabbit were similar (pHs= 7.5). Lowering luminal pH from 7.5 to 3.5 in opossum decreased pHsto 4.2 ± 0.16, a value significantly higher than pH of perfusate, whereas in rabbit this maneuver decreased pHsto 3.69 ± 0.08, a value not significantly different from pH of perfusate. In opossum but not in rabbit, addition of carbachol to the serosal solution increased basal pHsto 7.8 ± 0.1 and significantly blunted the decline in pHson perfusion with acidic Ringer solution (pH 3.5), with pHsfalling to 5.6 ± 0.45. The effect of carbachol on surface buffering was inhibited by prior treatment with atropine. Luminal acidification to pH 2.0 in opossum (as in rabbit) abolished the lumen-to-surface pH gradient even after addition of serosal carbachol. We conclude that the presence of submucosal glands in esophagus contributes through bicarbonate secretion to creation of a lumen-to-surface pH gradient. Although this gradient can be modulated by carbachol, its capacity to buffer (and therefore to protect) the epithelial surface against back-diffusing H+is limited and dissipated at pH 2.0.

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50

Widdicombe, Jonathan H. y Jeffrey J. Wine. "Airway Gland Structure and Function". Physiological Reviews 95, n.º 4 (octubre de 2015): 1241–319. http://dx.doi.org/10.1152/physrev.00039.2014.

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Submucosal glands contribute to airway surface liquid (ASL), a film that protects all airway surfaces. Glandular mucus comprises electrolytes, water, the gel-forming mucin MUC5B, and hundreds of different proteins with diverse protective functions. Gland volume per unit area of mucosal surface correlates positively with impaction rate of inhaled particles. In human main bronchi, the volume of the glands is ∼50 times that of surface goblet cells, but the glands diminish in size and frequency distally. ASL and its trapped particles are removed from the airways by mucociliary transport. Airway glands have a tubuloacinar structure, with a single terminal duct, a nonciliated collecting duct, then branching secretory tubules lined with mucous cells and ending in serous acini. They allow for a massive increase in numbers of mucus-producing cells without replacing surface ciliated cells. Active secretion of Cl−and HCO3−by serous cells produces most of the fluid of gland secretions. Glands are densely innervated by tonically active, mutually excitatory airway intrinsic neurons. Most gland mucus is secreted constitutively in vivo, with large, transient increases produced by emergency reflex drive from the vagus. Elevations of [cAMP]iand [Ca2+]icoordinate electrolyte and macromolecular secretion and probably occur together for baseline activity in vivo, with cholinergic elevation of [Ca2+]ibeing mainly responsive for transient increases in secretion. Altered submucosal gland function contributes to the pathology of all obstructive diseases, but is an early stage of pathogenesis only in cystic fibrosis.

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