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)

We studied binding of serotonin to protein(s) derived from rat basophil leukemia (RBL) cells and mast cells. We found two types of serotonin binding protein in RBL cells. These proteins differed from one another in molecular weight and eluted in separate peaks from sephadex G-200 columns. Peak I protein (KD = 1.9 X 10(-6) M) was a glycoprotein that bound to concanavalin A (Con A); Peak II protein (KD1 = 4.5 X 10(-8) M; KD2 = 3.9 X 10(-6) M) did not bind to Con A. Moreover, binding of [3H]serotonin to protein of peak I was sensitive to inhibition by reserpine, while binding of [3H]serotonin to protein of peak II resisted inhibition by that drug. Other differences between the two types of binding protein were found, the most significant of which was the far more vigorous conditions of homogenization required to extract peak I than peak II protein. Neither peak I nor peak II protein resembled the serotonin binding protein (SBP) that is found in serotonergic neurons of the brain and gut. Electron microscope radioautographic analysis of the intracellular distribution of [3H]serotonin taken up in vitro by RBL cells or in vivo by murine mast cells indicated that essentially all of the labeled amine was located in cytoplasmic granules. No evidence for a pool in the cytosol was found and all granules were capable of becoming labeled. The presence of two types of intracellular serotonin binding proteins in these cells may indicate that there are two intracellular storage compartments for the amine. Both may be intragranular, but peak I protein may be associated with the granular membrane while peak II protein may be more free within the granular core. Different storage proteins may help to explain the differential release of amines from mast cell granules.
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PMID:Serotonin storage pools in basophil leukemia and mast cells: characterization of two types of serotonin binding protein and radioautographic analysis of the intracellular distribution of [3H]serotonin. 711 96

The soluble granule chymase, rat mast cell protease-II (RMCP-II), is abundantly expressed in intestinal mucosal mast cells (MMC) but its function is not known. One hypothesis is that RMCP-II degrades the epithelial basement membrane and promotes the loss of enterocytes typically associated with type I hypersensitivity reactions in the rat. To test this hypothesis more directly, ex vivo perfusion of the cranial mesenteric artery and jejunal lumen was used to monitor the anaphylactic release of RMCP-II and its effects on mucosal permeability and epithelial integrity. Within 2 min of intravascular challenge with soluble adult Nippostrongylus brasiliensis worm antigen there was a 1,000-fold (P < 0.02) increase in the concentration of RMCP-II in the vascular perfusate from the jejunum of Nippostrongylus-sensitized rats but not the controls. Similarly, translocation of RMCP-II into the gut lumen increased 10-fold (P < 0.02) after 2 min only in worm antigen-challenged immune rats. Using an identical protocol, but incorporating Evans blue-labeled human serum albumin (EB-HSA) in the vascular perfusate, the timing of the release of RMCP-II into the two compartments was very similar to the first experiment and furthermore the translocation of EB-HSA increased 18-fold (P < 0.05) after 4 min in sensitized rats challenged with worm antigen. To examine the effects of RMCP-II more directly 1 mg of the highly purified chymase was introduced into the cranial mesenteric artery in ex vivo perfused normal rats. A significant (P < 0.05) 70-fold increase in concentration of RMCP-II in jejunal perfusate occurred after 6 min. In a repeat dose-response experiment, infusion of 0.375, 0.75, or 1.5 mg of RMCP-II, together with EB-HSA, established that the cumulative amounts of RMCP-II and EB-HSA translocated from the vasculature to the gut lumen in each perfusion (during the 10-min period of RMCP-II infusion) were significantly correlated. Analysis of intestinal perfusates by SDS-PAGE and by Western blotting using monoclonal anti-RMCP-II antibody confirmed that there was a concomitant translocation of both the protease and EB-HSA into the gut lumen. Histological evaluation of the mucosa failed to reveal any significant morphological change in any of the experiments. The rapid development of macromolecular leak, its association with the translocation of RMCP-II, and the absence of gross epithelial lesions, suggest for the first time that a mast cell granule chymase increases epithelial permeability via a paracellular route and implies that the substrate may be a protein, or proteins, in the epithelial junctional complex.
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PMID:Release of the mucosal mast cell granule chymase, rat mast cell protease-II, during anaphylaxis is associated with the rapid development of paracellular permeability to macromolecules in rat jejunum. 750 33

Histamine exhibits various biological effects in inflammatory and immunological reactions. To further define its potential role in allergic enteropathy and inflammatory bowel disease, both gut mucosal histamine levels and histamine release from endoscopic biopsy samples were measured. Tissue histamine content resulted from addition of the released amount of histamine and the remaining part of tissue histamine. The results demonstrate highly elevated mucosal histamine levels of the large intestine in allergic enteropathy. In inflammatory bowel disease histamine content and secretion were found to be significantly increased particularly in affected mucosa of Crohn's disease and ulcerative colitis than in unaffected tissue or in healthy controls. These findings give strong evidence that mast cell mediators like histamine play a role in the pathogenesis of these diseases. Mucosal histamine is thus concluded to contribute to the immuno-inflammatory reactions of the intestine found in these disease states and to reflect the degree of colonic inflammation in Crohn's disease and ulcerative colitis.
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PMID:Mucosal histamine content and histamine secretion in Crohn's disease, ulcerative colitis and allergic enteropathy. 754 99

The ability of four drugs with anti-allergic action to modulate the uptake of bystander protein, lactulose/rhamnose permeability ratios and mast cell activation was studied in rats presensitized with egg albumin in alum and challenged intraduodenally with the same antigen. Beclomethasone dipropionate (BDP) and nedocromil both significantly reduced the uptake of the bystander protein, bovine serum albumin (P < 0.002 and P > 0.02 respectively). BDP also significantly reduced sugar permeability (P < 0.01). In animals with elevated lactulose/rhamnose permeability ratios we confirmed our earlier observation of a significant correlation between levels of the specific mucosal mast cell protease Rat Chymase II (RChyII-previously known as RMCPII) and the sugar ratios. None of the drugs had any influence on the levels of mast cell protease II released following challenge and there was no correlation between the histological light microscopic appearance of the mast cells and the experimental treatment administered. Our results suggest that in the gut the pharmacological effect of anti-allergic drugs may be complex. Some, such as nedocromil, appear to act only on the mechanisms underlying increased protein uptake whereas others, such as BDP, appear to abrogate both increased protein uptake and increased sugar permeability.
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PMID:Experimental intestinal hypersensitivity. Effect of four anti-allergic drugs on protein uptake, permeability to sugars and mucosal mast-cell activation. 755 48

Nitric oxide (NO.) plays a central role in the physiology of the gastrointestinal tract and its response to critical illness. Potential sources of NO. in the gut include: intrinsic intestinal tissue (mast cells, epithelium, smooth muscle, neural plexus), resident and/or infiltrating leukocytes (neutrophils, monocytes), reduction of luminal gastric nitrate, and denitrification by commensal anaerobes. The brain and endothelial isoforms of nitric oxide synthase are expressed under resting conditions, whereas inflammatory stimuli are required for the induction of the inducible type. Under resting conditions, mucosal perfusion is regulated by NO. derived from the vascular endothelium of the mesenteric bed. During inflammation, excessive NO. production from the inducible synthase may contribute to mucosal hyperemia. Coordination of peristalsis and sphincteric action is mediated by the release of NO., which acts as the principal neurotransmitter of the nonadrenergic, noncholinergic enteric nervous system. Alterations in bowel motility, such as ileus, result from excessive concentrations of NO. generated during endotoxicosis and inflammatory bowel disease. The role of NO. in the regulation of salt and water secretion is poorly understood. Endotoxin-induced inhibition of gastric acid secretion appears to be mediated by the action of NO. on parietal cells. NO. may protect the gastrointestinal mucosa from a variety of stimuli (caustic ingestion, ischemia, ischemia/reperfusion injury, early endotoxic shock) by maintaining mucosal perfusion, inhibiting neutrophil adhesion to mesenteric endothelium, blocking platelet adhesion, and preventing mast cell activation. Excessive NO., however, may directly injure the mucosa. Barrier function of the intestinal mucosa is protected by NO. in the early stages of injury, when neutrophil adhesion, ischemia, and mast cell activation are relevant. Inhibition of NO. synthesis ameliorates barrier dysfunction during more advanced stages of inflammation, when activation of inducible NOS yields toxic concentrations of NO.. At high concentrations, NO. disrupts the actin cytoskeleton, inhibits ATP formation, dilates cellular tight junctions, and produces a hyperpermeable state. Selective inhibition of the inducible isoform of NOS and maintenance of the constitutive types may be therapeutic.
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PMID:Nitric oxide in the gut. 758 76

Both human and mouse c-kit ligand induced differentiation of human mast cells in a long-term culture of the mononuclear cells of umbilical cord blood. Growth factor activity for human mast cells present in conditioned medium of BALB/3T3 fibroblasts was due to mouse c-kit ligand. Recombinant c-kit ligand induced differentiation and proliferation of mast cell progenitors in early stages of culture. However, apparent selective growth of mast cells by c-kit ligand in cord blood cell cultures is mainly due to the effect of the cytokine to selectively maintain survival of immature mast cells. Electron microscopic analysis indicated that human mast cells developed by c-kit ligand were similar to human mast cells in the lung and gut mucosa, while those developed in coculture of cord blood cells with Swiss albino/3T3 fibroblasts were similar to skin mast cells. This conclusion was supported by the fact that the majority of mast cells developed by c-kit ligand contained only tryptase in their granules, whereas those developed in the cocultures contained both tryptase and chymase. It was also found that mast cells developed by c-kit ligand were immature even after culture for 14 weeks. Nevertheless, these cells express Fc epsilon RI, and could be sensitized with human IgE for anti-IgE-induced release of histamine, prostaglandin D2, and leukotriene C4.
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PMID:Development of human mast cells from umbilical cord blood cells by recombinant human and murine c-kit ligand. 767 63

The onset and severity of anaphylactic reactions in the rat have so far been related to Pavlovian conditioning, previous exposure to stress, and pretreatment with opioid agonists and antagonists. In this study, we compared two strains of rats derived from the same genetic pool (one outbred, Wistar, and one inbred, Wistar-Kyoto) for their susceptibility to anaphylactic shock (AS). In Experiment 1, baseline differences in the overt behavior of the two strains were established. In Experiment 2, following sensitization to ovalbumin, rats of both strains were challenged with antigen by either the intraperitoneal or the intragastric route. Wistar-Kyoto rats were more susceptible to the induction of AS as evidenced by a more pronounced drop in rectal temperature and greater intensity of clinical signs, although there was no evidence for strain-related differences in IgE titres. Experiment 3 replicated and extended the findings of Experiment 2. Again, Wistar-Kyoto rats were found to be more susceptible to the induction of AS. In addition to a greater drop in rectal temperature and intensity of clinical signs, more pronounced changes in gut function were found in the Wistar-Kyoto strain. This was indicated by an elevation of basal short-circuit current (an indication of the transport tone of the tissue mounted in the Ussing chambers). Most importantly, there was a strong linear relationship between measures of overt behaviour and various physiological indices of AS. This finding indicates that the same genetic basis may be responsible for the observed strain-related differences in behavior and susceptibility to AS, and that variations in nonimmunological factors of mast cell activation may also contribute to the observed differences in the susceptibility to anaphylactic reactions.
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PMID:Strain-related difference in susceptibility to anaphylactic shock correlates with measures of spontaneous activity. 769 19

Nitric oxide (NO.) plays a central role in the Physioliology of the gastrointestinal tract and its response to critical illness. Potential sources of NO. in the gut include: intrinsic intestinal tissue (mast cells, epithelium, smooth muscle, neural plexus), resident and/or infiltrating leukocytes (neutrophils, monocytes), reduction of luminal gastric nitrate, and denitrification by commensal anaerobes. The brain and endothelial isoforms of nitric oxide synthase are expressed under resting conditions, whereas inflammatory stimuli are required for the induction of the inducible type. Under resting conditions, mucosal perfusion is regulated by NO. derived from the vascular endothelium of the mesenteric bed. During inflammation, excessive NO. production from the inducible synthase may contribute to mucosal hyperemia. Coordination of peristalsis and sphincteric action is mediated by the release of NO., which acts as the principal neurotransmitter of the nonadrenergic, noncholinergic enteric nervous system. Alterations in bowel motility, such as ileus, result from excessive concentrations of NO. generated during endotoxicosis and inflammatory bowel disease. The role of NO. in the regulation of salt and water secretion is poorly understood. Endotoxin-induced inhibition of gastric acid secretion appears to be mediated by the action of NO. on parietal cells. NO. may protect the gastrointestinal mucosa from a variety of stimuli (caustic ingestion, ischemia, ischemia/reperfusion injury, early endotoxic shock) by maintaining mucosal perfusion, inhibiting neutrophil adhesion to mesenteric endothelium, blocking platelet adhesion, and preventing mast cell activation. Excessive NO., however, may directly injure the mucosa. Barrier function of the intestinal mucosa is protected by NO. in the early stages of injury, when neutrophil adhesion, ischemia, and mast cell activation are relevant. Inhibition of NO. synthesis ameliorates barrier dysfunction during more advanced stages of inflammation, when activation of inducible NOS yields toxic concentrations of NO.. At high concentrations, NO. disrupts the actin cytoskeleton, inhibits ATP formation, dilates cellular tight junctions, and produces a hyperpermeable state. Selective inhibition of the inducible isoform of NOS and maintenance of the constitutive types may be therapeutic.
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PMID:Nitric oxide in the gut. 770 93

Sudden reperfusion of the gut following prolonged ischemia can itself have more deleterious consequences than the ischemia alone. Studies of vasodilator factors influencing the increased flow on reperfusion are therefore of importance. In the present study, a possible role of histamine in the postischemic flow response was examined after a period of total segmental ischemia. The artery supplying the terminal ileum was occluded in anesthetized dogs. Ischemia of 30 min duration was followed by a 30 min reperfusion period (control postischemic flow response), and the arterial blood flow to the segment was measured. After the control postischemic flow response, one of the following drugs was administered intravenously: histamine H1-or H2-blockers (tripelennamine, .5 mg/kg, cimetidine, 10 mg/kg, ranitidine, 2 mg/kg), cromolyn (a mast cell stabilizer, 25 mg/kg), and aminoguanidine (a diamine oxidase blocker, 50 mg/kg). The 30 min ischemia-30 min reperfusion cycle was then repeated (test postischemic flow response). A 30 min mesenteric ischemia-reperfusion period is reproducible once without a significant change in its hemodynamic parameters. The duration and volume of the postischemic flow response were significantly decreased by cimetidine, ranitidine, or cromolyn, and were increased by aminoguanidine. Tripelennamine did not affect the postischemic vasodilator response. At the onset of reperfusion, a release of endogenous histamine occurs from the gut, originating mainly from mast cells. It is proposed that histamine participates in the postischemic flow response through the H2-receptors.
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PMID:Role of histamine in the intestinal flow response following mesenteric ischemia. 774 71

We analysed the cytokine profile of a T cell subset (CD4+ CD45 RC-) that confers protection against Trichinella spiralis infection in rats. These CD4+ cells are generated in the gut and appear in the thoracic duct lymph within 72 h after infection. Cytokine mRNA levels for IL-2, IL-3, IL-4, IL-5, IL-10 and IFN-gamma and functional cytokine secretion for IL-4, IL-5, IFN-gamma, TNF-alpha and mast cell differentiation activity were tested in vitro following stimulation with T. spiralis antigens. Compared to a non-protective T cell population (CD4+ CD45 RC+ or CD8+), also isolated from the same thoracic lymph, no significant differences were observed in the levels of mRNA for IL-2, IL-3, IL-4, IL-5, IL-10 or IFN-gamma in the protective CD4+ CD45 RC- cells. However, analysis of the cytokine activities in culture supernatant of these T cell subsets following 24 h stimulation in vitro with T. spiralis antigens showed that significant IL-4 and IL-5 activity but little IFN-gamma or TNF-alpha was secreted by the protective CD4+ CD45- RC- cells. Whereas the non-protective CD4+ CD45 RC+ cells secreted significant levels of IL-4, IFN-gamma, mast cell differentiating activity and TNF-alpha but little IL-5 activity. Non-protective CD8+ cells were found to secrete IL-4 but not IL-5. Production of IL-4 was essentially equal for both protective and non-protective T cell subsets. These findings suggest that the presence or absence of IFN-gamma secretion, rather than IL-4 alone, determines whether a T cell subset has protective activity against T. spiralis infection in rats.
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PMID:Cytokine profile of protective anti-Trichinella spiralis CD4+ OX22- and non-protective CD4+ OX22+ thoracic duct cells in rats: secretion of IL-4 alone does not determine protective capacity. 780 64


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