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)

Although the mechanism underlying hypoxic pulmonary vasoconstriction remains undefined, various reports have suggested that mast cells and cell-derived mediators may be important in the production of this phenomenon. We investigated the effect of reducing oxygen tension on the release from human lung fragments of the mast cell-derived mediators histamine, prostaglandin (PG) D2 and peptide leukotrienes, as well as the release of the largely non-mast cell-derived mediators PGE2, PGF2 alpha, prostacyclin metabolite (6-keto-PGF1 alpha) and the thromboxane A2 metabolite (thromboxane B2). The effect of reducing oxygen tension on both basal mediator release and release triggered by goat antihuman immunoglobulin E was studied. Reducing pO2 of buffer in which lung fragments were placed from 161 to 54 mm Hg resulted in no spontaneous release of histamine, PGD2 or peptide leukotrienes. However, hypoxia had a marked effect on mediator release triggered by goat antihuman immunoglobulin E. Although net histamine release was relatively unaffected (control 13.9 +/- 2.7%, hypoxic 12.7 +/- 2.1%), hypoxic treatment resulted in an 89% inhibition of PGD2 release (control 47.7 +/- 17.4 ng/g of lung, hypoxic 5.26 +/- 1.91 ng/g of lung) and an 81% inhibition of peptide leukotriene release (control 22.5 +/- 7.6 ng/g of lung, hypoxic 4.37 +/- 2.4 ng/g of lung). Similar inhibition was seen for non-mast cell-derived mediators, including PGF2 alpha, prostacyclin metabolite and thromboxane B2, and probably for PGE2. We conclude that hypoxic treatment of human lung fragments in vitro results in no spontaneous release of preformed or newly formed mediators but that it markedly alters mediator release after goat antihuman immunoglobulin E triggering.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mediator release from human lung under conditions of reduced oxygen tension. 242 80

Prostaglandin (PG) D2 and histamine concentrations have been measured in blood draining cold-challenged forearm skin in patients with cold urticaria. Local venous concentrations of both histamine and PGD2 rose in four patients who developed a whealing response. Plasma histamine concentration increased from a mean resting value of 0.24 +/- 0.09 (SD) ng/ml to peak values of 16.9 to 96.6 ng/ml. Resting concentrations of PGD2 were below the limit of detection (5 pg/ml) in three patients and 62 and 27 pg/ml in the fourth. Peak plasma PGD2 concentration after challenge ranged from 166 to 279 pg/ml. Time course of histamine and PGD2 release was similar with peak concentrations at 6 and 10 minutes, respectively. The maximum clinical response occurred between 10 and 20 minutes after challenge. Our findings demonstrate that PGD2 is produced in association with mast cell degranulation in man, but the amount, relative to histamine, is low. Despite its high potency in production of inflammatory effects, PGD2 probably has only minor direct effects in cold urticaria, although it may act to potentiate other mediators.
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PMID:Prostaglandin D2 and histamine release in cold urticaria. 242 56

Large numbers of functional mast cells were obtained by bronchoalveolar lavage (BAL) of Macaca arctoides monkeys that had been infected with the nematode Ascaris suum. These lavage cells, of which 21% were mast cells, released histamine, LTC4, and PGD2 in a concentration-dependent fashion when challenged with ascaris antigen or antibody to human IgE. However, there was no release of histamine when these cells were challenged with compound 48/80. The amount of mediator released was highly dependent on the sensitivity of the cells to immunologic challenge, but was generally in the range of 2 to 5 micrograms histamine (30 to 70% of total), 20 to 80 ng LTC4, and 100 to 300 ng PGD2 per 10(6) mast cells when maximally challenged. Other eicosanoids measured were released only in much smaller quantities. Maximal values were 4 ng LTB4, 2 ng PGE2, and approximately 10 to 20 ng PGF2 alpha per 10(6) mast cells. The amount of LTC4 and PGD2 released correlated with the release of histamine, the calculated regression line indicating that 18 ng LTC4 and 50 ng PGD2 were released per microgram of histamine released. This correlation suggests that the majority of the LTC4 and PGD2 released was probably mast cell-derived. Further support for this conclusion was given by the observation that when lavage cells were fractioned on continuous Percoll gradients, the ability to release LTC4 and PGD2 on immunologic challenge coincided with the peak of mast cells.
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PMID:Characterization of primate bronchoalveolar mast cells. I. IgE-dependent release of histamine, leukotrienes, and prostaglandins. 243 Oct 48

As described in the preceding companion paper, bronchoalveolar lavage (BAL) of the primate Macaca arctoides infected with the nematode Ascaris suum yields a population of cells containing a high proportion of mast cells (21%). Nedocromil sodium, a new drug undergoing clinical evaluation for the treatment of reversible obstructive airways disease, inhibited the release of histamine, LTC4, and PGD2 from these cells challenged with antigen (with IC30 values of 2.1 X 10(-6) M, 2.3 X 10(-6) M, and 1.9 X 10(-6) M, respectively) and with anti-human IgE (IC30 values of 4.7 X 10(-6) M, 1.3 X 10(-6) M, and 1.3 X 10(-6) M, respectively). Cromolyn sodium was essentially inactive. Histamine release from rat peritoneal mast cells induced by anti-rat IgE was, however, inhibited by both nedocromil sodium and cromolyn sodium with IC30 values of 1.1 X 10(-6) M and 5.5 X 10(-7) M, respectively. Both compounds induce phosphorylation of a 78,000 m.w. protein in the rat peritoneal mast cell in the absence of any stimulus at the same concentrations as those required to inhibit histamine release stimulated by anti-IgE. This event may be part of a feedback mechanism to limit degranulation. Nedocromil sodium and cromolyn sodium were equipotent in their ability to inhibit anti-IgE-induced histamine release from rat peritoneal mast cells, but differed markedly in their ability to inhibit histamine release from macaque BAL cells.
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PMID:Characterization of primate bronchoalveolar mast cells. II. Inhibition of histamine, LTC4, and PGD2 release from primate bronchoalveolar mast cells and a comparison with rat peritoneal mast cells. 243 Oct 49

The release of prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), and histamine induced by antigen and compound 48/80 was studied using an in vitro model of anaphylaxis in guinea pig skin. Abdominal skin from ovalbumin-sensitized guinea pigs was cut into 0.5-1.0 mm-thick slices which were incubated in Tyrode solution at 37 degrees C with or without either ovalbumin or 48/80. Released PGD2 and PGE2 were measured by radioimmunoassay and gas chromatography-mass spectrometry, respectively. Release of PGD2 was detectable at 2 min after challenge (50 micrograms/ml ovalbumin), reaching a maximum at about 15 min. Histamine release was more rapid, achieving 50% of maximum at about 4 min compared to about 7 min for PGD2. In 11 experiments incubation with ovalbumin (50 micrograms/ml for 10 min) induced a significant 6-fold increase in PGD2 compared to unchallenged controls (399 +/- 53 and 67 +/- 19 ng/g dry weight skin, respectively; mean +/- SEM) and a net 47.2% histamine release. In contrast, a smaller (27%) rise in PGE2 was found. Indomethacin (14 microns) completely suppressed evoked PGD2 and PGE2 synthesis without evident effect on histamine release, suggesting that the release of histamine in this model is not dependent on prostaglandin production. The mast cell degranulating agent compound 48/80 (50 micrograms/ml) released significant amounts of PGD2 (340 +/- 86 ng/g skin compared to 89 +/- 30 ng/g for control skin, n = 5) but had no appreciable effect on PGE2. These results show that guinea pig skin can synthesize significant quantities of PGD2 in anaphylactic reactions. Prostaglandin D2 produced in acute allergic reactions in skin in vivo may contribute to the inflammatory reaction, either directly or in synergism with other mediators.
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PMID:Prostaglandin D2 release by guinea pig skin during in vitro anaphylaxis induced by antigen and compound 48/80. 243 54

Human lung parenchymal mast cells displayed both specific and nonspecific desensitization. The kinetics of both release and desensitization were approximately equal to 3 times faster than human basophils, but a similar relationship between release and desensitization suggests similar biochemistries in basophils and mast cells. Arachidonic acid metabolite (PGD2 and LTC4) release was slower to desensitize (t1/2 of 8 min) than histamine release (t1/2 of 3 min), the ratio of which is similar to the ratio observed in basophils. Ionophore A23187-induced release was unaffected by desensitization to anti-IgE antibody, and calcium-45 uptake was inhibited by desensitization, suggesting that desensitization inhibits the early post-cross-linking "influx" of calcium that is necessary for mediator release in mast cells. In contrast to the above similarities in basophil and mast cell desensitization, mast cell desensitization, unlike that of basophils was not inhibited by diisopropylfluorophosphate.
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PMID:Basic characteristics of human lung mast cell desensitization. 243 88

Immunologic activation of purified human lung mast cells (HLMC) and basophils with anti-IgE induced histamine release but failed to elicit any changes in cAMP levels. In contrast, histamine release and monophasic rises in cAMP were observed in both rat peritoneal mast cells (RPMC) challenged with concanavalin A (73% enhancement over basal cAMP 20 sec after activation) and a cultured mouse bone marrow-derived mast cell (PT18 cell line) passively sensitized with dinitrophenol-specific IgE and stimulated with antigen (39% increase above basal at 15 sec). The adenylate cyclase activators isoprenaline, prostaglandin E2 (PGE2), and forskolin and the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) all induced elevations in cAMP levels in both basophils and HLMC. In basophils, PGE2 and isoprenaline produced approximately twofold increases in cAMP that were maximal at 1 min and decayed thereafter. Forskolin and IBMX produced threefold increases in cAMP that peaked 10 min after activation and persisted for up to 20 min. In HLMC, isoprenaline provoked a rapid monophasic fourfold increase in cAMP that was maximal at 1 min after addition. Levels of cAMP subsequently declined but remained significantly elevated over resting levels for up to 30 min. PGE2, forskolin, and IBMX all produced approximately threefold rises in HLMC cAMP that peaked around 5 min and persisted for 30 min. In both the basophil and HLMC, agonist-induced elevations in cAMP correlated well with the inhibition of mediator release. In basophils, the order IBMX greater than forskolin greater than PGE2 greater than isoprenaline held for both the inhibition of histamine and leukotriene C4 release and the augmentation of cAMP levels. In HLMC, individual agonists elevated cAMP levels to similar degrees and inhibited the release of histamine, leukotriene C4, and PGD2 to comparable extents, although the release of the arachidonate metabolites was generally more sensitive to the inhibitory actions of these agonists. These results suggest that elevations in cAMP, in both the basophil and HLMC, are associated with the inhibition of mediator release but not the initiation of the secretory process.
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PMID:Regulation of human basophil and lung mast cell function by cyclic adenosine monophosphate. 244 82

The clinical features of systemic mastocytosis have been ascribed to mast cell-dependent mediators, but there have been no studies of their release from isolated cells. We have investigated the release of histamine and eicosanoids from isolated spleen cells obtained from tissue of a mastocytosis patient undergoing therapeutic splenectomy. Dispersed cell preparations contained lymphocytes 65.9%, monocytes/macrophages 22.3%, neutrophils 9.9%, mast cells 1.1%, and eosinophils 0.8%; upon challenge with 0.1-3.0 microM A23187 they released histamine much greater than PGD2 greater than TXB2 greater than LTB4 greater than LTC4 approximately equal to LTD4 greater than LTE4. With immunological activation of passively sensitized cells, histamine and PGD2 release had similar dose-response characteristics, but TXB2, LTC4, LTD4, and LTE4 release differed in reaching maximum at 50 micrograms/ml and declining at 125 micrograms/ml anti-human IgE. Percoll centrifugation separated most of the histamine-containing cells to the middle of the gradient, but they were refractory to release with 0.3 microM A23187 or 50 micrograms/ml anti-IgE. Spontaneous release of histamine from these cells was not abnormally high (1.3%-4.5%). Electron microscopy of tissue sections revealed large numbers of mast cells with empty granules. It is possible that the refractory cells observed are such mast cells where intracellular histamine is no longer granule-associated. Most net histamine and PGD2 release was confined to cells at the bottom of the gradients (1.078-1.09 g/ml), although some release of PGD2 occurred near the top (1.05-1.058 g/ml). There was a significant correlation between the net release of histamine and PGD2 with both immunological (r = 0.92; n = 16) and A23187 (r = 0.97, n = 14) activation. These studies provide evidence for a link between PGD2 and histamine release in mastocytosis spleen cells.
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PMID:The immunoglobulin E- and calcium-dependent release of histamine and eicosanoids from human dispersed mastocytosis spleen cells. 245 Jan 44

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

Mast cells of human skin, but not lung, adenoids, tonsils, or intestine, release histamine in response to substance P, vasoactive intestinal polypeptide, and somatostatin. The substance P receptor of skin mast cells is not of the NK-1, NK-2 or NK-3 subtypes of smooth muscle. Time course and calcium dependency of release by peptides differed from anti-IgE. With anti-IgE, the molar ratios of histamine:PGD2:LTC4 generated by skin mast cells was 1,000:25:2, whereas with substance P these ratios were 1,000:1:0.1. Similar results were obtained with the other neuropeptides. The ability of peptides to stimulate skin mast cell histamine release suggests a mechanism whereby their release from dermal nerve endings is coupled to changes in microvasculature.
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PMID:Interaction of neuropeptides with human mast cells. 246 22


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