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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

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

Human lung mast cells were obtained from pulmonary tissue of normal individuals and patients with chronic bronchitis or emphysema by enzymatic dispersion. Based on their density two mast cell subtypes, a formalin-sensitive (FS) and a formalin-insensitive (FI) cell type, could be separated. Although differences in anti-IgE-induced histamine release could be demonstrated for the mast cell subtypes of normal individuals, these experiments could not be performed for both mast cell subtypes from both patient groups. LTC4 and PGD2 release could be demonstrated for the FS- and FI-mast cell respectively. The release of PGD2 from FI-mast cells of patients with chronic bronchitis was enhanced as compared with normal subjects.
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PMID:Mediator release from human lung mast cell subtypes in chronic bronchitis and emphysema. 247 45

Nicotinic acid (niacin) is a B vitamin which is also a potent hypolipidemic agent. However, intense flushing occurs following ingestion of pharmacologic doses of niacin which greatly limits its usefulness in treating hyperlipidemias. Previous studies have demonstrated that niacin-induced flushing can be substantially attenuated by pre-treatment with cyclooxygenase inhibitors, suggesting that the vasodilation is mediated by a prostaglandin. However, the prostaglandin that presumably mediates the flush has not been conclusively determined. In this study we report the finding that ingestion of niacin evokes the release of markedly increased quantities of PGD2 in vivo in humans. PGD2 release was assessed by quantification of the PGD2 metabolite, 9 alpha, 11 beta-PGF2, in plasma by gas chromatography mass spectrometry. Following ingestion of 500 mg of niacin in three normal volunteers, intense flushing occurred and plasma levels of 9 alpha, 11 beta-PGF2 were found to increase dramatically by 800, 430, and 535-fold. Levels of 9 alpha, 11 beta-PGF2 reached a maximum between 12 and 45 min. after ingesting niacin and subsequently declined to near normal levels by 2-4 hours. Levels of 9 alpha, 11 beta-PGF2 in plasma correlated with the intensity and duration of flushing that occurred in the 3 volunteers. Release of PGD2 was not accompanied by a release of histamine which was assessed by quantification of plasma levels of the histamine metabolite, N tau-methylhistamine. This suggests that the origin of the PGD2 release is not the mast cell. Only a modest increase (approximately 2-fold) in the urinary excretion of the prostacyclin metabolite, 2,3-dinor-6-keto-PGF1 alpha, occurred following ingestion of niacin and no increase in the excretion of the major urinary metabolite of PGE2 was found. These results indicate that the major vasodilatory PG released following ingestion of niacin is PGD2. The fact that markedly increased quantities of PGD2 are released suggests that PGD2 is the mediator of niacin-induced vasodilation in humans.
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PMID:Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid. 247 89

Glucocorticoids are potent anti-inflammatory drugs that are widely used in the treatment of allergic disorders. Their actions are often species specific or cell-type specific. Previous studies have demonstrated that glucocorticoids inhibit mediator release from mast cells derived from the peritoneum of mouse or rat and from guinea pig lung, but not those residing in human lung parenchymal tissue. In the present study, we have analyzed the effect of overnight culture with dexamethasone (10(-6) to 10(-7)M) on the subsequent IgE-dependent release of mediators from human mast cells derived from airway tissue, intestine, and skin. Airway tissue was passively sensitized with antigen-specific, IgE-rich serum during the culture period and subsequently challenged with ragweed antigen E. Skin and intestinal mast cells were challenged with anti-IgE. Histamine and immunoreactive LTC4 and PGD2 release was monitored in all experiments. Prostaglandin E release was quantitated in the experiments using airway tissue. Dexamethasone treatment failed to inhibit the release of mast cell mediators from all three tissues, but it inhibited the antigen-induced release of immunoreactive PGE from other cells residing in airway tissue. These results confirm earlier studies of the effects of glucocorticoids on human lung parenchymal mast cells, but contrast with the inhibitory effects of steroids observed in murine mast cells and human basophils.
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PMID:Dexamethasone does not inhibit the release of mediators from human mast cells residing in airway, intestine, or skin. 247 59

Mast cells and macrophages were isolated from human lung tissues by using density gradient centrifugation, cell sorter, and adherence techniques. Passively sensitized mast cells in the absence of exogenous arachidonic acid (AA) released leukotriene (LT)C4, LTD4, PGD2, and thromboxane-B2 when challenged with Ag, and in the presence of AA, released 5-hydroxyeicosatetraenoic acid (HETE) and 15-HETE in addition to the above metabolites. Passively sensitized macrophages did not release significant amounts of AA metabolites when challenged with Ag. However, these cells released LTB4, LTC4, LTD4, LTE4, 5-HETE, PGE2 and 6-keto-PGF1 alpha when co-incubated with activated mast cells. During co-incubation, mast cells also generated greater amount of AA metabolites than when they were activated alone. The stimulatory action of mast cells on macrophages was shown to be due to the extracellular factor(s) present in the supernatant of the activated mast cells. Both heat and trypsin inhibited the biologic activity of mast cell-derived stimulatory factor. In addition, extraction of mast cells' materials with chloroform or ether showed no activity associated with the organic phase, suggesting it possibly possesses a protein nature, such as peptides, protease, or peptidase. These results suggest that mast cell-macrophage interaction might be important in the generation of multiple mediators in the airways during immediate hypersensitivity reactions.
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PMID:Mast cell mediators stimulate synthesis of arachidonic acid metabolites in macrophages. 249 26


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