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)

Clostridium difficile toxin A (Tx-A) mediates secretion and inflammation in experimental enterocolitis. Intravital video microscopy was used to define the mechanisms that underlie the inflammatory reactions elicited by direct exposure of the microvasculature to Tx-A. Leukocyte adherence and emigration, leukocyte-platelet aggregation, and extravasation of FITC-albumin were monitored in rat mesenteric venules exposed to Tx-A. Significant increases in leukocyte adherence and emigration (LAE) and albumin leakage were noted within 15-30 min of Tx-A exposure. These responses were accompanied by mast cell degranulation and the formation of platelet-leukocyte aggregates. The Tx-A-induced increases in LAE and albumin leakage were significantly attenuated by pretreatment with either monoclonal antibodies (mAbs) directed against the leukocyte adhesion glycoproteins, CD11/CD18, intercellular adhesion molecule-1, and P-selectin (but not E-selectin) or with sialyl Lewis x, a counter-receptor for P-selectin. The mast cell stabilizer, lodoxamide, an H1- (but not an H2-) receptor antagonist, and diamine oxidase (histaminase) were also effective in reducing the LAE and albumin leakage elicited by Tx-A. The platelet-leukocyte aggregation response was blunted by an mAb against P-selectin, sialyl Lewis x, and the H1-receptor antagonist. These observations indicate that Tx-A induces a leukocyte-dependent leakage of albumin from postcapillary venules. Mast cell-derived histamine appears to mediate at least part of the leukocyte-endothelial cell adhesion and platelet-leukocyte aggregation by engaging H1-receptors on endothelial cells and platelets to increase the expression of P-selectin. The adhesion glycoproteins CD11/CD18 and intercellular adhesion molecule-1 also contribute to the inflammatory responses elicited by toxin A.
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PMID:Clostridium difficile toxin A-induced microvascular dysfunction. Role of histamine. 796 37

Changes in blood-nerve barrier (BNB) integrity and nerve conduction were assessed in rat tibial nerves in which mast cell degranulation was induced by intraneural injection of Compound 48/80 (C48/80). BNB permeability changes were quantitated by the endoneurial accumulation of Evan's blue-labelled albumin (EBA). Over 24 h following intraneural injections, nerves receiving saline showed a 6-fold increase in endoneurial extravasated EBA compared to non-injected nerves. Injection of 250 ng C48/80 produced a similar level of EBA accumulation as saline injections. Increasing the C48/80 dose to 1 microgram produced twice the EBA accumulation as control saline injections and a 12-fold increase over non-injected nerves. Tibial nerves injected with these C48/80 doses showed completely normal nerve conduction. In contrast, increasing the dose to 5 micrograms C48/80 induced, again, increased EBA accumulation over lower doses, but also significant axonal degeneration indicated by profound decreases in compound muscle action potential amplitudes measured with nerve stimulation distal to the injection site. Co-injection of Leupeptin and neutralizing anti-TNF-alpha antibodies with C48/80 failed to mitigate conduction abnormalities suggesting a direct toxic effect of C48/80 on nerve fibres. Time-kinetic studies showed rapid restoration of BNB integrity 24-48 h after injections in all nerves, but at these timepoints C48/80 injected nerves still showed significantly increased BNB permeability compared to nerves injected with saline. Neural mast cell stimulation in the absence of a primed immune response can produce profound temporary changes in blood-nerve barrier permeability and endoneurial fluid composition without affecting nerve conduction.
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PMID:Effects of mast cell degranulation on blood-nerve barrier permeability and nerve conduction in vivo. 796 79

Hexahydrophthalic anhydride (HHPA) is a component of some epoxy resin systems. A high fraction of HHPA-exposed workers display nasal symptoms, and some of them have specific serum antibodies. To test the pathogenetic relevance of the antibodies nasal challenge tests were performed with a conjugate of HHPA and human serum albumin (HSA) at three increasing concentrations. Eleven subjects, who were IgE-sensitized against HHPA (positive in RAST and in skin-prick test against the HHPA-HSA conjugate), and who reported work-related nasal symptoms, had a significant increase of nasal symptoms and a decrease of nasal inspiratory peak flow after the challenges. The symptoms were associated with specific serum IgE, but with IgG. Further, significant increases were found in eosinophil and neutrophil counts, and in levels of tryptase, and albumin, whereas no clear rise was recorded for eosinophil cationic protein in nasal lavage fluid. Nine subjects, who were not sensitized, but who complained of work-related nasal symptoms, and 11 subjects, who were not sensitized and had no symptoms, displayed no significant change in any of these parameters. It is concluded that the symptoms in some of the workers were caused by an IgE-mediated mast cell degranulation, followed by an inflammatory reaction, engaging eosinophil and neutrophil cells.
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PMID:Nasal challenge shows pathogenetic relevance of specific IgE serum antibodies for nasal symptoms caused by hexahydrophthalic anhydride. 808 55

Leukocyte-endothelial cell adhesion and an altered metabolism of endothelial cell-derived nitric oxide (NO) have been implicated in the microvascular dysfunction associated with ischemia/reperfusion (I/R). The objective of this study was to determine whether NO donors can attenuate the reperfusion-induced increase in venular albumin leakage via an effect on leukocyte-endothelial cell adhesion. Leukocyte adherence and emigration as well as albumin extravasation were monitored in single postcapillary venules in rat mesentery subjected to 20 minutes of ischemia followed by 30 minutes of reperfusion. This I/R protocol elicits significant leukocyte adherence and emigration as well as a profound albumin leakage response. Superfusion of the mesenteric microcirculation with the NO donors sodium nitroprusside, spermine-NO, and SIN1 significantly reduced the I/R-induced leukocyte adherence/emigration and albumin leakage in postcapillary venules, whereas neither spermine nor the NO synthase inhibitor NG-nitro-L-arginine methyl ester affected the I/R-induced responses. Platelet-leukocyte aggregation and mast cell degranulation were also observed in the postischemic mesentery, and the responses were also attenuated by the NO donors. Plasma nitrate/nitrite levels in the superior mesenteric vein were significantly reduced by I/R. The results of this study indicate that I/R-induced microvascular dysfunction (albumin leakage) is attenuated by NO and that the protective effect of NO donors may be related to their ability to reduce leukocyte-endothelial cell and leukocyte-platelet interactions and/or mast cell degranulation.
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PMID:Modulation of ischemia/reperfusion-induced microvascular dysfunction by nitric oxide. 811 46

Sarcoidosis affecting the lungs may cause obstructive and/or restrictive lung function impairment. The bronchial reactivity is related to the release of histamine from the mast cells. Upon activation mast cells also release tryptase. This enzyme may activate latent collagenase and thus possibly contribute to the fibrosis formation observed in sarcoidosis. We analyzed the bronchoalveolar lavage fluid (BALF) from 13 nonsmoking and untreated patients with sarcoidosis and from 30 healthy volunteers (18 smokers) with regard to the number of mast cells and the tryptase concentration. Concomitantly albumin, fibronectin and hyaluronan were measured as markers of the inflammatory reaction in the alveoli and interstitium. The number of mast cells was higher (p < 0.001) in patients with sarcoidosis than in controls. Also, the concentration of tryptase was significantly higher in patients (225.3 +/- 83.9 [SEM] mU/L) compared to nonsmoking and smoking controls (34.7 +/- 7.8 and 44.7 +/- 13.0 mU/L, respectively; p < 0.01 for both). In addition, the concentrations of albumin, fibronectin and hyaluronan were higher in patients with sarcoidosis compared to the nonsmoking controls (p < 0.001 for all). However, there was no relationship between either the mast cell number or the tryptase concentration and the lung function parameters (VC, TLC, FEV1, FEV%, DLCO). As our patients did not show any functional signs of bronchial obstruction (FEV1 91.7% +/- 13.3 [SD] and FEV% 99.5% +/- 6.4 of predicted) the lack of correlation is not surprising. The high concentrations observed in the BALF of the noncellular components may just reflect an ongoing inflammatory process that may resolve or, if exaggerated, lead to fibrosis.
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PMID:Elevated levels of tryptase in bronchoalveolar lavage fluid from patients with sarcoidosis. 813 9

The aim of this study was to evaluate the cellular and biochemical characteristics of the bronchoalveolar lavage (BAL) fluid in patients with farmer's lung disease (FLD). Total cell numbers in BAL fluids from patients with FLD (n = 30) were significantly higher than in normal subjects (n = 7; p < 0.01), and differential cell counts were significantly different. Lymphocytes were the most numerous cell type in BAL fluids from patients with FLD (65.4 +/- 2.5 percent vs 6.8 +/- 0.5 percent), and analysis of lymphocyte subsets revealed increased percentages of CD3+ and CD8+ cells (91.8 +/- 0.9 percent vs 68.8 +/- 3 percent, p < 0.01, and 54.3 +/- 3.1 percent vs 30.1 +/- 3.2 percent, p < 0.01, respectively). A marked increase in mast cell numbers, as revealed by the specific alcian blue/safranin staining, was observed in patients with FLD (4.2 +/- 0.57 percent, n = 12, vs 0.18 +/- 0.04 percent, n = 7, p < 0.001). Histamine levels in BAL supernatants were increased in patients with FLD (mean = SEM, 4.4 +/- 0.8 ng/ml vs 0.9 +/- 0.1 ng/ml; median, 2.4 ng/ml vs 0.9 ng/ml, p < 0.01), and correlated positively with mast cell numbers and percentages (r = +0.63, p < 0.03, and r = +0.69, p < 0.02, respectively); conversely, a negative correlation was found between histamine levels and CD8+ lymphocyte percentages (r = -0.48, p < 0.01). Raised neutrophil percentages (5.1 +/- 0.8 vs 0.5 +/- 0.18, p < 0.05) and albumin concentrations (29.2 +/- 3.9 mg/dl vs 3.4 +/- 1.3 mg/dl, p < 0.01) were also found in patients with FLD. These findings show that increased numbers of mast cells, lymphocytes, and neutrophils can be found in BAL fluids of patients with FLD. The increased histamine levels in the supernatants of BAL fluids indicate that mast cells are activated. These data allow us to postulate a role for mast cell accumulation and histamine release in the inflammatory process of FLD.
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PMID:Mast cell and histamine involvement in farmer's lung disease. 816 47

The present study was performed to investigate whether the increased negativity of interstitial fluid pressure (Pif) observed after intravenous injection of dextran could be mediated via mast cell degranulation induced by C48/80 and polymyxin B sulfate. Increased negativity of Pif, concomitant with edema formation and increased albumin extravasation, was seen with both substances. However, the two substances differed in that polymyxin B sulfate induced less negativity in Pif and a larger but transient increase in capillary albumin extravasation and interstitial fluid volume. Total tissue water (TTW) increased from 2.11 to 2.71 ml/g dry wt 10 min after polymyxin B and returned to control level at 30 and 60 min. Injection of C48/80 increased TTW to 2.68 ml/g dry wt at 30 min, and TTW was still elevated at 60 min. Albumin extravasation followed a similar pattern; polymyxin B sulfate increased albumin extravasation from < 0.08 to 1.18 ml/g dry wt during the first 5 min after administration. C48/80 was less potent, and maximal albumin leakage was seen after 10-25 min (0.25 ml/g dry wt). The observations demonstrate the importance of the interstitium and the loose connective tissues as "active" participants in the edema-generating process and suggest an interaction with the structural components of the interstitium, as well as an important role for the mast cells in the chain of events creating increased negativity of Pif.
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PMID:Increased negativity of interstitial fluid pressure in rat trachea after mast cell degranulation. 833 40

Intestine from rats sensitized to egg albumin (EA) antigen responds to EA challenge with an increase in short-circuit current (Isc), indicative of predominantly chloride secretion. Here, we have examined the role of interferon alpha/beta (IFN alpha/beta) in the control of this event. Muscle-stripped jejunal segments from sensitized rats, mounted in Ussing chambers, displayed a reduced response to EA-challenge in the presence of IFN alpha/beta (100-1000 U/ml), when the cytokine was incubated with the tissue for > or = 60 min; serosal and luminal responses were significantly reduced by ca.32-47% and ca.50-80%, respectively. Preabsorption with an anti-IFN alpha/beta antibody abolished this inhibition. IFN alpha/beta did not influence the secretory response of the tissues to histamine, serotonin, bethanechol, or forskolin, suggesting that IFN alpha/beta does not affect the epithelium directly. IFN alpha/beta had no effect on Isc changes induced by electrical transmural stimulation of mucosal nerves in the tissue, nor did neuronal blockade with tetrodotoxin influence the action of IFN alpha/beta. These data indicate that the effect of IFN alpha/beta is not neuronally mediated. The normal anti-secretory actions of diphenhydramine (H1-antagonist) and piroxicam (cylooxygenase inhibitor) upon antigen-activation of mast cells, were not apparent in the presence of IFN alpha/beta. This suggests that IFN alpha/beta inhibits intestinal hypersensitivity by acting directly on mast cells. This hypothesis was confirmed by inhibition of antigen-induced release of the specific mucosal mast cell marker, rat mast cell protease II, in tissues treated with IFN alpha/beta. These findings suggest that IFN alpha/beta can function as an intestinal anti-inflammatory agent by stabilizing mucosal mast cells.
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PMID:Inhibition of antigen-induced secretion in the rat jejunum by interferon alpha/beta. 834 70

Altered intestinal motility and diarrhea are features of food protein-induced intestinal anaphylaxis in the conscious rat. These experiments were performed to determine the mediator(s) responsible for jejunal circular smooth muscle contraction during this response. Hooded-Lister rats were sensitized by intraperitoneal injection of 10-micrograms egg albumin, and controls were sham-sensitized with saline. Fourteen days later the contractility of the circular muscle in jejunal segments (mucosa intact) was examined in standard tissue baths in response to antigen (Ag) or other agents. While control and sensitized tissues contracted in similar fashion in response to stretch, bethanechol, histamine, or 5-hydroxytryptamine (5HT), Ag contracted only the segments of sensitized animals. The contractile response was: (1) specific to the sensitizing Ag, as bovine serum albumin did not induce contraction and (2) could be passively transferred with serum containing specific immunoglobulin E antibody (IgE-Ab). Concanavalin A, which degranulates both mucosal and connective tissue-type mast cells, and compound 48/80, which degranulates only connective tissue-type mast cells produced contractile responses. Ag-induced contraction was significantly inhibited by the mucosal and connective tissue-type mast cell stabilizer doxantrazole, but not the connective tissue mast cell stabilizer disodium cromoglycate. Diphenhydramine and cimetidine together significantly inhibited histamine-induced contraction, but failed to effect the Ag-induced contraction in sensitized tissues. While the contractile response to 5HT was reduced in the presence of methysergide (5HT1-receptor antagonist), cinanserin (5HT2-receptor antagonist), and ICS 205-930 (5HT3-receptor antagonist), only cinanserin significantly inhibited the contractile response to Ag. Indomethacin significantly inhibited Ag-induced contraction. Ag-induced contraction was resistant to atropine and tetrodotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mediation of anaphylaxis-induced jejunal circular smooth muscle contraction in rats. 844 68

In vivo uptake of the probe 51Cr-labeled EDTA from the jejunum of egg albumin (EA)-sensitized rats was compared with controls at baseline and after intraluminal antigen challenge. Probe recovery in blood was 60-80% greater in sensitized animals during the baseline period, suggesting that sensitization resulted in increased intestinal permeability. Sensitized, but not control, rats demonstrated a 15-fold increase in 51Cr-EDTA uptake after intraluminal antigen; no change occurred with an unrelated protein. Macromolecular recovery was also enhanced in sensitized animals, since serum levels of immunoreactive EA were elevated 14-fold compared with controls. Antigen challenge was accompanied by biochemical (protease release) and morphological (reduced numbers) evidence of mast cell degranulation in sensitized rats. The neurotoxin tetrodotoxin (applied directly to ligated jejunal segments) inhibited EA-induced uptake of 51Cr-EDTA and antigen. In isolated jejunum from sensitized rats, tetrodotoxin reduced secretory responses to luminal, but not serosal, antigen. These results indicate that neural factors may influence the uptake of molecules from the gut lumen during intestinal anaphylaxis.
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PMID:Intestinal permeability in allergic rats: nerve involvement in antigen-induced changes. 847 49


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