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)

The effect of valinomycin on both, mast cell histamine release and on calcium (45Ca)-uptake processes was examined. Pleural and peritoneal mast cells were purified in isotonic Percoll (pH = 7) and mixed populations were used in the experiments. Valinomycin (10(-9)-10(-5) M) stimulated histamine release in isolated rat mast cells when the incubation medium contained high K+ concentrations (Tris-K+ with 150 mM K+), but not in other media such as Tris-Na+ (120 mM Na+) or Tris-sucrose (300 mM sucrose). In contrast, in the absence of valinomycin, elevated K+ levels in the external environment did not activate mast cell secretion. Optimum response in valinomycin-treated mast cells was obtained when the cells were incubated for 60 min. Also valinomycin (10(-5) M) induced substantial inhibition of 45Ca-uptake while lower doses (10(-9)-10(-7) M) did not affect or only slightly increased uptake. In this paper valinomycin is shown to be a degranulating agent eliciting mediator release in mast cells incubated in the presence of high K+ levels, which does not require extracellular calcium and inhibits 45Ca uptake. The possibility that valinomycin acts as a K+ ionophore, as in other secretory systems, is discussed.
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PMID:Valinomycin, a degranulating agent in rat mast cells which inhibits calcium-uptake. 245 99

Human synovium obtained at arthroplasty from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were characterized by assessing mast cell morphology, content and function. Histological studies confirmed significant numbers of mast cells in both RA and OA synovium. Electron microscopic data support the morphologic similarity between human synovial mast cells and human mast cells in lung and intestine. Likewise, synovial mast cells do not appear to be functionally different from pulmonary or intestinal mucosal mast cells. Mast cell suspensions with a cellular histamine content of 4.3 +/- 0.5 pg/cell (mean +/- SEM) released histamine following provocation with anti-IgE and calcium ionophore but not compound 48/80, f-met peptide or bradykinin. Prostaglandin D2 (PGD2) and leukotriene C4 (LTC4) were also released in response to anti-IgE. Auranofin inhibited anti-IgE provoked histamine, PGD2 and LTC4 release while gold sodium thiomalate, cromolyn and indomethacin had no effect on histamine release. Theophylline inhibited anti-IgE induced histamine release only at concentrations greater than or equal to 10(-3) M. Our study argues against functional or morphologic mast cell heterogeneity of human intestinal, lung and synovial origin and suggests that mast cells may have a pathogenic role in both RA and OA.
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PMID:Characterization of human synovial mast cells. 246 48

The mast cell activator, compound 48/80, produced increased vascularity and tortuosity of blood vessels in the chorioallantoic membrane (CAM) of ten day old embryonic chicks. Application of 400 micrograms/ml resulted in rapid mast cell granule release, observed after 1 min at both light and electron microscopy level, and resulted in the greatest increase (69%) in CAM mesenchymal vessels. The half-maximal dose was 38.6 micrograms/ml, computer-derived from the dose-response data. It is apparent that a single episode of mast cell degranulation is sufficient to induce vessel growth over several days, but the fact that a sublethal dose is required for maximum stimulation casts doubt on its biological significance. This pattern of response resembles that previously found by us with histamine and has not been found so far with commercial heparins and chemically modified derivatives. In contrast, a sublethal dose of porcine intestinal sodium heparin results in an antiangiogenic effect on the ectodermal capillary plexus.
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PMID:Effect of the mast cell activator compound 48/80 and heparin on angiogenesis in the chick chorioallantoic membrane. 246 53

Epirubicin induces an important noncytotoxic release of histamine from rat peritoneal cells in vitro. This exocytotic response is inhibited by sodium cromoglycate, similarly to that elicited by the classic mast cell secretagogue, compound 48/80. Mast cells obtained from the peritoneal cavities of rats treated with epirubicin in vivo were extensively degranulated; in contrast, samples obtained from rats pretreated with sodium cromoglycate showed normal appearing mast cells. When injected i.p., immediately before the antineoplastic agent, cromolyn significantly improved the survival time and the microscopic appearance of myocardial tissues of epirubicin-treated mice. The results indicate that histamine release could play an important role in the pathogenesis of anthracycline-induced cardiotoxicity.
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PMID:Amelioration of 4'-epidoxorubicin-induced cardiotoxicity by sodium cromoglycate. 246 9

The effect of a putative Na+/H+ exchange inhibition on histamine and [14C]arachidonic acid ([14C]AA) release has been examined in rat peritoneal mast cells, using either addition of amiloride or removal of extracellular Na+. The cells were stimulated by non-immunological agents, i.e. calcium ionophore A23187, nerve growth factor (NGF), thapsigargin and compound 48/80. On the basis of the results obtained, a possible role for Na+/H+ exchange in rat mast cell secretion is discussed.
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PMID:Effect of amiloride on arachidonic acid and histamine release from rat mast cells. 247 28

Various human lymphokines such as semipurified human interleukin 3 (IL 3), recombinant human IL 3, granulocyte colony stimulating factor (G-CSF), and recombinant human interleukin 4 (IL 4) stimulated growth of human bone marrow cells, but from all these factors tested, only IL 3 by itself was able to cause an increase in histamine content. Fibroblast monolayers as well as factors in their supernatants also increased proliferation and histamine content of bone marrow cells. Concentrated supernatants (Mr greater than 10,000) also inhibited cell proliferation and induced histamine content. The same fraction concentrated on a Mr cut-off greater than 50,000 enhanced cell growth and the total histamine content per culture. Thus, fibroblast supernatants contained both growth promoting and inhibitory factors. However, using the rat basophilic leukemia (RBL) cell line as a test system for such fibroblast-derived differentiation factors, we showed that if cell proliferation was inhibited, histamine content was also enhanced. Furthermore, certain drugs known to inhibit cell division, such as sodium butyrate or hydroxyurea, were also found to cause an increase in histamine content of RBL cells. Thus, our data demonstrate that basophil/mast cell differentiation, in terms of augmentation of cellular histamine levels, may be achieved by exposure to certain growth-inducing cytokines, factors inhibiting proliferation or pharmacological agents which inhibit cell proliferation.
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PMID:Factors influencing proliferation and histamine content of cultured human bone marrow cells. 247 28

To understand better the role of mast cell secretory products in the genesis of inflammation, a system was developed for in vitro degranulation of human mast cells in skin organ cultures. Within 2 hr after morphine sulfate-induced degranulation, endothelial cells lining microvessels adjacent to affected mast cells expressed an activation antigen important for endothelial-leukocyte adhesion. Identical results were obtained when other mast cell secretagogues (anti-IgE, compound 48/80, and calcium ionophore A23187) were used. Induction of this antigen was abrogated by preincubation with cromolyn sodium, an inhibitor of mast cell secretion, and by antiserum to tumor necrosis factor alpha. These findings indicate that degranulation of mast cells activates dermal endothelium through tumor necrosis factor-dependent mechanisms. This event may be critical to the elicitation phase of cutaneous inflammation.
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PMID:Degranulation of human mast cells induces an endothelial antigen central to leukocyte adhesion. 247 33

Peripheral nervous system mast cells degranulate early in the development of experimental allergic neuritis (EAN). This degranulation is associated with the release of vasoactive amines, chemoattractants and myelinolytic proteases which could provide a focus for inflammatory demyelination. To further assess the importance of mast cell degranulation in the development of EAN, we have treated Lewis rats inoculated with peripheral nervous system myelin and complete Freund's adjuvant, with nedocromil sodium, an anti-inflammatory drug with mast cell stabilizing properties. Treatment with nedocromil sodium (100-150 mg/kg), 3 times daily, starting on day 7 post-inoculation, significantly decreases the incidence and the severity of the disease. Histological examination of sciatic nerves confirms the absence of subclinical disease in successfully treated animals. The possible mode of action of the drug is discussed.
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PMID:Treatment of experimental allergic neuritis with nedocromil sodium. 247 61

The mechanism of action of the "mast cell stabilizers" sodium cromoglycate and FPL-52694 as protective agents against ethanol-induced gastric mucosal damage was investigated in the rat. Using an ex vivo gastric chamber model, various concentrations (10-80 mg/mL) of the two agents were applied to the gastric mucosa prior to exposure to 40% ethanol. Both agents significantly reduced ethanol-induced damage in a dose-dependent manner. When given orally (80 mg/kg) both agents significantly reduced gastric damage induced by subsequent oral administration of absolute ethanol. Pretreatment with indomethacin did not significantly affect the protection afforded by FPL-52694, but did cause a partial reversal of the protective effect of sodium cromoglycate. Changes in gastric leukotriene C4 synthesis did not correlate with the protective effects of the two agents. Both mucosal and connective tissue mast cell numbers were significantly reduced following oral ethanol administration. In the groups pretreated with FPL-52694 or sodium cromoglycate, mucosal mast cell numbers were not significantly different from those in rats not treated with ethanol. Furthermore, the connective tissue mast cell numbers were significantly lower than in ethanol-treated control rats, despite a greater than 95% reduction of ethanol-induced hemorrhagic damage. These results therefore suggest that stimulation of gastric prostaglandin synthesis is not important in the mechanism of action of FPL-52694, and neither agent appears to reduce damage through a mechanism related to effects on gastric leukotriene C4 synthesis. The present studies further suggest that the protection afforded by pretreatment with sodium cromoglycate or FPL-52694 may be unrelated to effects of these agents on the connective tissue mast cell population in the stomach.
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PMID:Reduction of ethanol-induced gastric damage by sodium cromoglycate and FPL-52694. Role of leukotrienes, prostaglandins, and mast cells in the protective mechanism. 250 42

Sodium cromoglycate is a drug widely used in the treatment of bronchial asthma. In vitro and animal models show that its effect is related to mast cell stabilization and to a direct action on inflammatory cells or the broncho-obstructive reflex. In man, sodium cromoglycate is able to prevent bronchoconstriction induced by a variety of stimuli including the 'late' reaction to allergen. It is also able to prevent the allergen-induced increase in hyperresponsiveness. Long-term therapeutic trials have confirmed its validity in the treatment of asthmatic patients.
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PMID:Sodium cromoglycate: a review. 250 49


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