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

Mast cells and basophils, although sharing many constitutive properties, are quite distinct in their development, functions and biological properties. Mast cell granules are composed of a macromolecular matrix of proteoglycan and neutral protease of which heparin and tryptase, respectively, are predominant. The distribution of the other major neutral protease, chymase, allows human mast cell subpopulations to be subdivided immunocytochemically. All human mast cells respond to IgE-dependent stimulation with the secretion of the preformed mediator, histamine, and the newly generated lipid-derived eicosanoids PGD2 and LTC4. Although amounts of these products vary between mast cells dispersed from different tissues, it is uncertain whether this reflects true heterogeneity. Mast cells of the human skin, but not those of other tissues, are sensitive to stimulation by substance P, compound 48/80 and other basic non-immunological stimuli. The mechanism of mediator secretion induced by these agents is distinct from that induced by IgE-dependent stimulation. However, the morphological characteristics of degranulation are similar, suggesting that the distinct biochemical pathways merge into a common pathway before effecting degranulation.
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PMID:Biological properties of human skin mast cells. 191 78

A long-term co-culture of mononuclear cells of human umbilical cord blood with mouse embryo-derived 3T3 fibroblasts resulted in the development of human mast cells. These mast cells are morphologically and functionally mature cells, containing 1.4-2.8 micrograms histamine per 10(6) cells and bear approximately 10(5) Fc epsilon RI per cell. The mast cells sensitized with human IgE released histamine upon challenge with anti-IgE. Electron-microscopic analysis of the cells showed that these cells were mature human mast cells, and clearly different from basophilic granulocytes. Most of the mast cells contained some granules with regular crystalline arrays and both tryptase and chymase, resembling human skin mast cells. When mononuclear cells of cord blood were seeded in a millicell insert which was placed on 3T3 fibroblasts monolayer, the number of mast cells developed in the millicell inserts was comparable to those developed in the co-culture of the same cord blood cells with 3T3 fibroblasts. Recent observations that mast cells developed in the presence of concentrated culture supernatants of 3T3 fibroblasts without fibroblasts feeder layers, confirmed that soluble factors released from 3T3 fibroblasts are essential and sufficient for the differentiation of human mast cell progenitors in vitro. Analysis of functional characteristics of cultured mast cells revealed that they respond to anti-IgE, Ca2+ ionophore A23187 and substance P for histamine release, but failed to respond to compound 48/80 and FMLP. Upon anti-IgE challenge, sensitized mast cells generated approximately 80 ng PGD2 per 10(6) cells, and approximately 50 ng of LTC4 per 10(6) cells but no detectable generation of LTB4.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro development and functions of human mast cells. 193 64

The characteristics of the acute and late human response to antigen in the upper and lower airways and in the skin is summarized in TABLE 2. This table makes it clear that while mast cells are responsible for the mediator release of the acute phase, eosinophils and basophils are the cells involved in the mediator release which occurs during the experimental late phase reaction. The pattern of mediators observed during the acute response is quite characteristic of the mast cell. Thus, in the nose, skin, and lungs, the acute response is characterized by significant increases in histamine, PGD2, tryptase, and sometimes LTC4. In the late phase reaction, the pattern of mediator release is characteristic of basophils and eosinophils, and includes histamine, LTC4 (where measurable), and eosinophil-derived proteins, without PGD2 or tryptase. Basophils have been identified at appropriate time-points in each model using morphologic and phenotypic criteria, and their numbers relate to the histamine levels. Finally, treatment with glucocorticosteroids, the most potent drugs available for treating chronic allergic inflammation, obliterates the late phase reaction and decreases both mediator release and the infiltration of eosinophils and basophils. Chronic allergic inflammation is now taken by both the pulmonary and immunologic community as a hallmark of asthma, and it can be stated without equivocation that the basophils are responsible for the mediator release observed in that response.
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PMID:The role of basophils in asthma. 195 78

Air-pouch-type inflammation was induced by injecting sodium carboxymethyl cellulose solution containing leukotriene C4 (LTC4, 3.20 x 10(-7) M, 0.2 micrograms/ml) and prostaglandin E2 (PGE2, 5.68 x 10(-6) M, 2.0 micrograms/ml), platelet-activating factor (PAF, 1 x 10(-6) M, 0.52 micrograms/ml), or 12-O-tetradecanoyl phorbol 13-acetate (TPA, 1.62 x 10(-6) M, 1.0 micrograms/ml) into an air pouch made on the dorsum of rats. Vascular permeability and tissue edema formation were significantly increased by injecting the phlogogen solution. The histamine level in the pouch fluid was dramatically increased by injecting TPA but not by LTC4 and PGE2, or PAF. Injection of isoproterenol or procaterol with the phlogogen solution produced dose-dependent suppression of both vascular permeability increase and tissue edema formation. However, the TPA-induced increase in the histamine level was not suppressed in parallel with the decrease of vascular permeability or tissue edema formation. These results indicate that beta-agonists suppress vascular permeability response and local tissue edema formation not by inhibiting mast cell degranulation, but by inhibiting the reactivity of the local vasculature to chemical mediators such as arachidonate metabolites, PAF, and histamine and serotonin released from mast cells.
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PMID:Suppression by adrenoceptor beta-agonists of vascular permeability increase and edema formation induced by arachidonate metabolites, platelet-activating factor, and tumor-promoting phorbol ester TPA. 197 74

Leukotrienes are potent proinflammatory mediators. Our understanding of their role in allergic rhinitis has increased, but further, extensive investigation is required. The sulfidopeptide LTs are generated during the immediate response to antigen provocation and are probably increased during the late inflammatory phase and during seasonal exposure. The source of LTC4 in the early allergic reaction includes the mast cell, but other cell types may also contribute. LTD4 causes nasal congestion and increased blood flow, but not sneezing or significant rhinorrhea. Studies in which LT generation was pharmacologically reduced support a role for these mediators in allergic rhinitis. There is now a need to evaluate the more potent, recently developed, LT antagonists in rhinitis. These agents should help establish the relative importance of LTs to the many other inflammatory mediators that are implicated in the pathogenesis of allergic rhinitis. Such knowledge will broaden and improve our choice of therapeutic modalities for this disease.
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PMID:The role of leukotrienes in allergic rhinitis: a review. 201 50

Tissue mast cells play a central role in immediate hypersensitivity reactions. The clinical manifestations of these reactions appear to be dependent, in large part, on the anatomic location of the stimulated mast cells and the type of mediators released. In vivo and in vitro studies indicate that the tissues in which mast cells reside may greatly influence their biochemical composition, expression of surface receptors, and response to potential stimuli. Although all human mast cells in different organs store similar concentrations of histamine, heparin, and tryptase, cutaneous mast cells appear to be the predominant source of mast cell-derived chymase. Furthermore, at the time of stimulation, human skin mast cells predominantly form PGD2, whereas lung and intestinal mast cells generate LTB4, LTC4, and PGD2. Functional studies indicate that human cutaneous mast cells differ from human lung, heart, and intestinal mast cells. Skin mast cells are responsive to a variety of immunologic and nonimmunologic stimuli in vitro, whereas human pulmonary, cardiac, and intestinal mast cells are relatively refractory to many of these stimulatory signals. Taken together, these observations indicate that mast cells may assume different, and possibly specialized, functions within a specific tissue. Such site-to-site variation potentially could have important clinical significance, to the extent that information gained from mast cells in one organ may not be applicable to a mast cell population in a different tissue. Furthermore, these differences among human mast cells may not be confined to their biochemical composition and responses to various stimuli, but also may extend to the effectiveness of different anti-allergic preparations. Therefore, these observations underscore the importance of continued detailed investigation of human mast cells from different anatomic sites.
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PMID:IgE and immediate hypersensitivity. 224 56

A cloned murine mast cell line designated MC9 expresses a 5-lipoxygenase activity when stimulated with the ionophore A23187. Upon addition of 0.5 microM ionophore, MC9 cells produce 270 +/- 43 pmoles 5-HETE, 74 +/- 40 pmoles 5,12 diHETEs and 65 +/- 31 pmoles LTC4/10(6) cells from 37 microM exogenously added [1-14C]arachidonic acid in two minutes. 5-HETE and 5,12-diHETES, including LTB4 were identified by GC/MS whereas LTC4 was confirmed by HPLC mobility, bio-assay, RIA and enzymatic transformation. The principal cyclooxygenase products were PGD2 and TxB2 (8.5 +/- 2.4 and 5.4 +/- 1.2 pmoles/10(6) cells respectively). Prostanoids were identified by comigration with authentic standards on two-dimensional thin layer chromatograms. Production of arachidonic acid lipoxygenase metabolites stimulated with ionophore proved relatively insensitive to removal of extracellular Ca+2 and chelation by EGTA. In addition, MC9 5-lipoxygenase required only low micromolar amounts of exogenous arachidonic acid for maximal activity. Whereas production of arachidonic acid metabolites lasted only two to five minutes, histamine release stimulated with ionophore was not initiated until 5 minutes (12 +/- 3% cellular histamine) and continued for 30 minutes (37 +/- 7% cellular histamine). Although these cells metabolize arachidonic acid differently from the classic peritoneal-derived mast cell, they resemble subpopulations found in certain tissues (such as mucosa) and should be useful in understanding the biochemistry of mast cell mediator release.
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PMID:Ionophore-stimulated lipoxygenase activity and histamine release in a cloned murine mast cell, MC9. 240 98

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


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