Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Excessive fluid and electrolyte secretion, resulting symptomatically in diarrhea, has been associated with mast cell activation in a variety of experimental and clinical settings. The present study has used a human colonic epithelial cell line to examine mechanisms underlying this phenomenon. Acute addition of mixed mast cell mediators (as a lysate of rat basophilic leukemia cells) to epithelial cells led to prompt and sustained chloride secretion. The response was partially inhibitable by an antihistaminic drug and an adenosine antagonist, suggesting that histamine, adenosine, and possibly other mediators are responsible for producing the acute effect. Supernatants from immunologically activated rat basophilic leukemia cells had similar effects. Chronic exposure of epithelial cells to the lysate mediator preparation, followed by washing, had no effect on their basal electrical or electrolyte-transporting properties. However, the chloride secretory response of the cells to subsequent addition of vasoactive intestinal peptide, carbachol, and heat-stable enterotoxin of Escherichia coli was significantly enhanced, whereas responses to an adenosine agonist or PGE1 were unaffected. This study has, therefore, demonstrated two ways in which mast cell mediators can directly influence intestinal epithelial cells to secrete more chloride and, hence, to enhance fluid secretion in the gut. The findings may be of relevance to our understanding of inflammatory diarrhea and may aid the development of novel therapies for this disorder.
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PMID:Immune-related intestinal chloride secretion. III. Acute and chronic effects of mast cell mediators on chloride secretion by a human colonic epithelial cell line. 165 Mar 88

Different doses of protamine sulphate (PS) given s.c. (at 12-h intervals) were tested for signs of non-specific toxicity measured as effect on body weight and small-gut proliferation as well as on mast-cell secretion and mast-cell-mediated mitogenesis in the mesenteric windows following i.p. injection of Compound 48/80, a potent mast cell secretagogue, in normal rats. In a non-toxic dose range, the effect of PS on mast-cell-mediated angiogenesis, effected by 48/80, was quantified as the number of vessels per mm of mesenteric window in histological sections at x 400. No intelligible dose-effect relationship was discernible between the dose of PS given and the effect on angiogenesis. Only in a tight interval, at 40 mg PS/kg but not at 20 or 60 mg PS/kg, was the angiogenesis statistically significantly suppressed. Hence, it was concluded that PS can be angiostatic but does not exert a more general angiostatic effect in the autogenous systems used.
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PMID:Protamine and mast-cell-mediated angiogenesis in the rat. 169 20

Inflammatory mediators from intestinal mast cells may serve as initiators of acute and delayed inflammation. Mast cell histamine release was measured in 19 patients with inflammatory bowel diseases using gut mast cells from enzymatically dispersed endoscopic forceps biopsy specimens of macroscopically inflamed and normal tissue. Mast cells and corresponding basophils were challenged with anti-IgE, anti-IgG, subclass anti-IgG4, and formyl-methionyl-leucyl-phenylalanine (FMLP) and results were compared with those from nine patient control subjects. The mast cell count in patients with ulcerative colitis was increased compared with that in control subjects and patients with Crohn's disease, and the mast cell count obtained from inflamed tissue was greater than that of normal tissue. The study also shows the heterogeneity of the responsiveness of the histamine releasing cells to various secretagogues. Thus, mast cells released 0.4 (0.0-2.0) (median (range)) ng histamine per sample at anti-IgE challenge, and basophils were also anti-IgE responsive. In contrast, mast cells did not respond to FMLP but the corresponding basophils did. Gut mast cells released 0.3 (0.0-1.0) (median (range)) ng histamine per sample at anti-IgG4 challenge; however, the corresponding basophils did not respond to anti-IgG4. In addition, the anti-IgG4 mediated histamine release was primarily confined to patients with inflammatory bowel disease. This study substantiates previous histopathological findings that mast cells may play a functional role in the inflammatory process of inflammatory bowel diseases and provides evidence for a possible role of subclass IgG4 as a reaginic antibody.
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PMID:Histamine release from gut mast cells from patients with inflammatory bowel diseases. 169 60

As part of an ongoing investigation of human mast cell heterogeneity, we have isolated, partially purified, and characterized the uterine mast cell and compared it with mast cells isolated from other organs. The average histamine content of myometrium and leiomyofibroma obtained from hysterectomies was 2.1 +/- 0.3 (mean +/- SEM) microgram/g of tissue (n = 10), and the histamine content of the two tissues did not differ significantly. A mild collagenase, hyaluronidase, and DNase digestion was used to disperse the uterine mast cells, with an average yield of 9.5% (range, 0 to 21%). The average histamine/uterine mast cell was 2.1 +/- 0.2 pg (n = 3), and 61 +/- 7% (n= 3) of the uterine mast cells survived overnight culture. Early purification efforts with Percoll gradients have yielded up to 80% pure uterine mast cells, with an average of 27 +/- 10% (n = 5). Uterine mast cells released histamine in response to the secretogogues anti-IgE and A23187 but did not respond to substance P or to the basophil secretogogues FMLP, C5a, and 12-O-tetradecanoylphorbol-13-acetate. After 1 microgram/ml anti-IgE stimulation, the uterine mast cell appeared to make significant quantities of PGD2 (89 +/- 26 ng/10(6) cells, n = 6) (p less than 0.05), as assayed by RIA. Simultaneously, leukotriene C4 release was 45 +/- 15 ng/10(6) cells, (n = 6) (p less than 0.05), as assayed by RIA. Combined gas-chromatography mass spectroscopy analysis of anti-IgE-stimulated cell supernatants confirmed the production of PGD2. In pharmacologic studies, isobutyl-methylxanthine and isoproterenol blocked anti-IgE-induced histamine release. The uterine mast cell is similar to the lung mast cell in terms of response to secretogogues and release of arachidonic acid metabolites. Ultrastructurally, the uterine mast cell contains scroll granules, crystal granules, combined granules, homogeneously dense granules, and large lipid bodies, many with focal lucencies within them. Particle granules, most frequently present in gut mast cells of mucosal origin, were absent from uterine mast cells. Although certain features are analogous to the ultrastructure of skin or lung mast cells, the combination of structures is distinctive for uterine mast cells.
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PMID:Human uterine mast cells. Isolation, purification, characterization, ultrastructure, and pharmacology. 171 65

Adult rainbow trout (Oncorhynchus mykiss) were injected intraperitoneally with capsaicin, substance P, serotonin, or a control of saline vehicle or bovine serum albumin (0.5 microgram/g body weight). Fish were sacrificed 30 min and 1, 2, and 4 h post-injection, the gut was dissected out, and a small section of the upper intestine was processed for electron microscopy. A significant proportion of eosinophilic granule cells (EGCs) of the intestine were in close association with non-myelinated neuronal bundles in all fish (4 fish per treatment and time period), but there was no significant difference between treatment or time, suggesting that the association was unaffected by these factors. Close examination of EGC ultrastructure showed that fish treated with capsaicin and substance P exhibited limited degranulation of the EGCs in the stratum compactum and extensive crinophagic-like degranulation in the lamina propria. Cells of the lamina propria contained characteristic multivesicular-like bodies. The degranulation was reminiscent of both mast cell degranulation and endocrine cell crinophagy. EGCs of fish treated with serotonin or a control were unaffected, suggesting that the serotoninergic neurons, believed to be involved in gut motility, were not responsible for degranulation. It is apparent that EGCs of the trout intestine may be under nervous control, as has been demonstrated previously for mammalian mast cells.
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PMID:Degranulation of eosinophilic granule cells induced by capsaicin and substance P in the intestine of the rainbow trout (Oncorhynchus mykiss Walbaum). 172 61

Intestinal mucosal mast cells (IMMCs) are closely apposed to nerves, which is consistent with other evidence suggesting that mast cells are innervated. Recent studies have indicated that coordinated changes in mast cell and nerve densities occur in the gut mucosa, during progressive fibrosis, but there is a lack of experimental evidence to support remodeling of intestinal nerve fibers as part of a disease process. Infection of rats with the nematode Nippostrongylus brasiliensis (Nb) results in an initial loss of stainable IMMCs, during an acute inflammatory phase, with subsequent mast cell hyperplasia. Accordingly, we employed the Nb model to look for structural neuroplasticity of intestinal mucosal nerves during inflammation. Immunocytochemical labeling of neurofilament subunits was very low in the jejunal mucosa of all animals, whereas neuron-specific enolase (NSE)-immunoreactive nerves were relatively abundant in control animals. The number of NSE-immunoreactive profiles increased approximately 2.5-fold by day 10 (d10) postinfection (p less than 0.01) and returned to near control values by d14. Immunoreactivity for B-50/GAP-43 was more extensive, labeling more than four times the number of nerves per villus, compared with NSE (p less than 0.0001). B-50 immunoreactivity decreased minimally (ca. 20%) by d7 postinfection, and then increased through control values between d10 and d21, to 30% greater than controls at d49 (p less than 0.05). Subclassification of the B-50-immunoreactive nerves according to cross-sectional area revealed a greater than twofold increase in the proportions of large fibers at d7 and d10. Subsequently, the proportions of small nerves were increased compared with controls. The fiber size changes were found to correlate with mast cell densities (r = -0.72 for large and r = 0.76 for small nerves). At d10, dilated B-50- and NSE-immunoreactive nerves predominated, and extraneuronal NSE was noted. Electron microscopy revealed that this was due to axonal dilation and degeneration. These data provide evidence for plasticity of intestinal mucosal nerve fibers during inflammation. This includes early degenerative and later regenerative phases that appear to correlate with mast cell densities. The phenotype of mucosal nerves in control animals suggests ongoing modeling of these fibers.
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PMID:Remodeling of B-50 (GAP-43)- and NSE-immunoreactive mucosal nerves in the intestines of rats infected with Nippostrongylus brasiliensis. 183 18

The study of mast cells and nerve fibres in routine biopsies of human oxyntic mucosa was performed with the use of microscopic and ultrastructural methods. Simultaneous visualization of mast cells with Alcian blue and nerves with anti S-100 antibody allowed to study contacts between these two elements of lamina propria. Approximately 17% of mast cells appose nerves in gastric mucosa, which is less than the number of such contacts in the gut reported by other authors. We have found no differences between histologically normal mucosa and gastritis in the aspect of the total number of mast cells per 1 mm2 of lamina propria, number of their contacts with nerves and the ratio of mast cells apposing nerves to the total amount of mast cells. The ultrastructural study revealed significant polymorphism of mast cell-neuron contacts as well as the absence of any specialized structures at the site of adhesion between these two types of cells. The mode of degranulation of mast cells suggests that they are actively engaged in the reaction to noxious stimuli challenging the oxyntic mucosa.
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PMID:Close contacts between mast cells and nerve fibres in the human oxyntic mucosa. 184 85

Mast cell degranulation in the gut causes mucus secretion, mucosal edema, and increased gut permeability and may be responsible for some of the symptoms and signs of inflammatory bowel disease. We have used a novel monoclonal antibody (AAI) against tryptase expressed exclusively in the granules of mast cells to enumerate mast cells in rectal biopsies in order to study the effect of inflammatory bowel disease and drug treatment upon rectal mast cell numbers. Rectal mast cell numbers are significantly reduced in inflammatory bowel disease patients taking corticosteroids (mean 4.95 cells/mm2) when compared with control patients (10.1, P less than 0.001) and inflammatory bowel disease patients not taking corticosteroids (9.7, P less than 0.001 Wilcoxon rank sum test). The reduction in mast cell counts was independent of the degree of inflammation or architectural distortion. There was a negative correlation between the dose of corticosteroids and mast cell count (r = 0.53, P less than 0.05 Spearman rank correlation), and the mast cell count was reduced within a few days of treatment and remained low throughout steroid therapy. Mucosal mast cell depletion may be an important mechanism of action of corticosteroids in inflammatory bowel disease.
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PMID:Corticosteroid treatment reduces mast cell numbers in inflammatory bowel disease. 197 67

Levels of intestinal mast cell protease (IMCP) were quantified in serum, gut tissue and in intestinal fluids taken from mice infected with Trichinella spiralis during primary and secondary infections. The ability to generate a mast cell response was dependent on the response phenotype of the mouse strain used. The mast cell response in rapid responder mice (NIH) occurred sooner and was more pronounced than in either intermediate (SWR) and low responder (B1O) mice. This pattern was also reflected in the concentration of IMCP found in various tissues examined. The correlations between IMCP concentrations in blood, and worm expulsion, are discussed.
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PMID:Functional correlations between mucosal mast cell activity and immunity to Trichinella spiralis in high and low responder mice. 208 10

Basal and stimulated changes in ion transport in vitro were examined in jejunal mucosa from rats during inflammation produced after infection with the nematode Nippostrongylus brasiliensis. The gut was acutely inflamed at days 7 and 10 when net secretion of Na+ and Cl- ions was evident. Serum levels of rat mast cell protease II were elevated, providing evidence for mast cell activation. In addition, the magnitude of the short-circuit current responses to electrical transmural stimulation of enteric nerves (but not to histamine in the presence of neural blockade) were significantly reduced (p less than 0.01) to 17%-33% of control values, suggesting abnormalities of mucosal nerves. Following worm expulsion, serum levels of rat mast cell protease II and ion transport returned to normal. However, mastocytosis was apparent in gut mucosa and parasite antigen stimulated net secretion. In the absence of antigen, short-circuit current responses to nerve stimulation were increased (to 122% of controls; p less than 0.05). These findings suggest that changes in mast cells and enteric nerves occur during inflammation in this model and implicate neural and mast cell interactions with the epithelium in producing the ion-transport abnormalities.
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PMID:Ion transport abnormalities in inflamed rat jejunum. Involvement of mast cells and nerves. 215 98


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