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)

Human bronchial epithelial cells were isolated from macroscopically normal bronchi obtained from lobectomy specimens. Cells were grown in nutrient F12 medium, and after the third or fourth subculture they were stimulated with arachidonic acid, histamine, leukotrienes (LT) C4, D4, or E4, prostaglandin (PG) D2, anti-IgE, acetylcholine, bradykinin, or phorbol myristate acetate (PMA). Neither mast cell mediators (i.e., histamine, LTC4, LTD4, LTE4, or PGD2) nor anti-IgE stimulated the release of arachidonic acid metabolites from the epithelial cells. However, arachidonic acid, acetylcholine, bradykinin, and PMA stimulated the release of 15-hydroxyeicosatetraenoic acid (15-HETE) as major and prostaglandin E2 (PGE2) as minor products. The maximal release of 15-HETE and PGE2 occurred in 1 h with arachidonic acid stimulation and in 2 h with other stimuli. Arachidonic acid at 30 microM caused the release of 258 +/- 76 ng and 29 +/- 15 ng (n = 12) of 15-HETE and PGE2, respectively, from 10 x 10(6) epithelial cells, whereas acetylcholine, bradykinin, or PMA caused the release of approximately 2- to 10-fold less 15-HETE and PGE2. These results demonstrate that human bronchial epithelial cells selectively generate 15-HETE as the predominant arachidonic acid product and PGE2 as a minor metabolite. The role of bronchial epithelial cells and their mediators in the pathogenesis of bronchial hyperresponsiveness needs further study.
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PMID:Release of 15-hydroxyeicosatetraenoic acid (15-HETE) and prostaglandin E2 (PGE2) by cultured human bronchial epithelial cells. 251 53

Metabolism of sulfidopeptide leukotrienes, leukotrienes (LT) C4 and D4 by rat peritoneal mast cells was studied. Rat peritoneal mast cells converted LTD4 to LTE4 but not LTC4 to LTD4. The LTD4-metabolizing activity was equally distributed on the cell surface and inside cells, but not released to the extracellular milieu even when a considerable portion of histamine and the secretory granule enzymes were released. Among various enzyme inhibitors examined, o-phenanthroline, a metal chelator, and dithiothreitol significantly suppressed the LTD4-metabolizing activity of mast cell. These results would suggest that some metalloenzyme located on the cell surface is involved in the conversion of LTD4 to LTE4 by rat peritoneal mast cells.
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PMID:Metabolism of leukotriene D4 by rat peritoneal mast cells. 254 77

To increase understanding of the effect of H1 antihistamines on the immediate response to nasal challenge with antigen, we performed two double blind, placebo-controlled, crossover studies using cetirizine and terfenadine. The subjects underwent nasal challenge with antigen after premedication with either cetirizine (20 mg QD for two days, n = 10), terfenadine (60 mg BID for 1 week, n = 12), or placebo for equivalent periods of time. We monitored the response to challenge by counting the number of sneezes and by measuring the levels of inflammatory substances in recovered nasal lavages. Compared with placebo, both antihistamines significantly reduced sneezing and the levels of recovered albumin and TAME esterase activity, suggesting that both reduced the expected increase in vascular permeability. With cetirizine, there was also a reduction in the levels of LTC4 (not measured in terfenadine studies) but not in those of recovered histamine and prostaglandin D2. These data suggest that cetirizine did not affect mast cell mediator release, that histamine release is due to the direct action of antigen stimulation and that leukotrienes are generated by cells in addition to mast cells. With terfenadine, there were significant reductions in the levels of histamine and kinins (not measured in cetirizine study) seen after nasal challenge with antigen. The reduction in kinins most likely reflects alteration in vascular permeability, whereas the effect on histamine presumably reflects inhibition of mast cell activation. When combined, these experiments demonstrate effects of H1 antihistamines on histamine release beyond those usually described, as well as differences between drugs within a single classification.
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PMID:The effects of H1 antihistamines on the early allergic response. 257 50

A cloned murine mast cell MC9 expresses phospholipase and lipoxygenase activity when stimulated with IgE and hapten. Addition of DNP-BSA to sensitized MC9 cells causes release of 58% of the cell histamine and 127 pmoles LTC4/10(6) cells. Prelabelling studies with [1-14C]-arachidonic acid showed that LTC4 production was proceeded by the release of arachidonic acid from membrane phospholipids. Approximately 8.7% of the cell arachidonic acid was released and half of this was converted to LTC4. The remaining radioactivity was converted to diHETES including LTB4 (15%), 5-HETE (10%), free arachidonic acid (10%), reesterified 5-HETE and arachidonic acid (8%) and prostaglandins (7%). This stimulation was dependent on hapten (DNP-BSA) and extracellular Ca++. Under identical conditions the calcium ionophore A23187 stimulated the release of 10.3% of the total cell arachidonic acid, and 51% of this was metabolized to LTC4. In addition the ionophore stimulated the release of 61% of the total cellular histamine.
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PMID:Antigenic stimulated release of arachidonic acid, lipoxygenase activity and histamine release in a cloned murine mast cell MC9. 257 93

A diagrammatic representation of the interactions between mediators of hypersensitivity and leukocytes in early, late-phase, and ongoing asthma is shown in Figure 1. Early phase or immediate reactions are largely the result of bronchoconstriction consequent to the release of mediators such as histamine, PGD2, LTC4/D4, and PAF. The principal mediator cell (MC) is the mast cell (although other IgE receptor-bearing cells such as the macrophage, eosinophil, and platelet might also be involved in this immediate response). The stimulus for mediator cell activation may be either immunologic (IgE-dependent) or nonimmunologic (i.e., changes in osmolarity as a result of the respiratory water loss associated with exercise-induced asthma). Late-phase reactions appear to be a consequence of infiltration with neutrophils (N), eosinophils (E), and macrophages (M phi). These cells are recruited and activated either by mast cell-associated chemotactic factors [such as LTB4, PAF, the eosinophil chemotactic factor of anaphylaxis (ECF-A), or high-molecular weight neutrophil chemotactic activity (NCA (HMW))] and/or "lymphokines" derived from T-helper cells (TH) which have been stimulated by antigen processed by the antigen-processing cells (APC). These mononuclear cell interactions are under the control of regulatory T cells [T suppressor (TS) cells] and it is speculated that the availability of these subsets may determine the magnitude of the late-phase response. Lymphokines and monokines which selectively activate neutrophils, eosinophils, and monocytes include LIF, EAF, and IFN-gamma, respectively. Macrophage-derived tumor necrosis factor (TNF) also amplifies the inflammatory response by its capacity to enhance eosinophil cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inflammatory cells in bronchial asthma. 270 38

We examined mucosal injury in the jejunum of the rat during infection with the nematode parasite, Nippostrongylus brasiliensis (Nb). Injury was documented morphologically (increase in crypt length with or without villus atrophy) and biochemically (activities of digestive or proliferative enzymes) and related to mast cell activation and leukotriene generation. At day 4 crypt length and thymidine kinase activity were increased; no changes in villus parameters were recorded. No evidence of mast cell activation was found and leukotriene levels in the mucosa were normal. At day 7, the gut was acutely inflamed and edema was present at the tips of the villi. This progressed to enterocyte detachment, resulting in villus atrophy with decreased activities of brush border enzymes. At this stage mucosal histamine was decreased and rat mast cell protease II (RMCP II) was increased in serum, indicating mast cell activation. In addition, mucosal leukotrienes (LTB4, LTC4, LTE4) were present in significant quantities. Following worm expulsion, the villus abnormalities resolved and serum RMCP II returned to normal. However, the crypt hyperplasia persisted. Our results suggest that during Nb infection at least two components of injury can be identified. One component, epithelial injury at the villus tips, may be related to activation of mucosal mast cells.
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PMID:Intestinal mucosal injury is associated with mast cell activation and leukotriene generation during Nippostrongylus-induced inflammation in the rat. 271 47

The experiments discussed above indicate that during immediate hypersensitivity reactions, macrophages are stimulated by mast cells to synthesize PGE2 and 6-keto-PGF1 alpha but not LTC4. The arachidonic acid utilized for these products is mobilized from the macrophages itself and not shuttled from the mast cells. The stimulus for the involvement of the macrophage does not appear to be a direct cell interaction between the two cell types or a soluble factor released by the mast cells. Since the profile of eicosanoids produced by macrophages when exposed to mast cell granules is similar to that observed in the contribution of macrophages to immediate hypersensitivity reactions, mast cell granules appear to be responsible for the recruitment of macrophages to this reaction.
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PMID:Nature of the mast cell-macrophage interaction in immediate hypersensitivity. 295 44

A diagrammatic representation of the interactions between mediators of hypersensitivity and leucocytes in early-, late-phase, and ongoing asthma is shown in Fig. 1. Early-phase or immediate reactions are largely the result of bronchoconstriction consequent to the release of mediators such as histamine, PGD2, LTC4/D4 and PAF. The principal mediator cell (MC) is the mast cell (although other IgE receptor-bearing cells such as the macrophage, eosinophil and platelet might also be involved in this immediate response). The stimulus for mediator cell activation may be either immunologic (IgE-dependent) or non-immunologic (i.e. changes in osmolarity as a result of the respiratory water loss associated with exercise-induced asthma). Late-phase reactions appear to be a consequence of infiltration with neutrophils (N), eosinophils (E) and macrophages (MO). These cells are recruited and activated either by mast cell-associated chemotactic factors [such as LTB4, PAF, the eosinophil chemotactic factor of anaphylaxis (ECF-A) or high molecular weight neutrophil chemotactic activity (NCA (HMW]] and/or "lymphokines" derived from T helper cells (TH) which have been stimulated by antigen processed by the antigen processing cells (APC). These mononuclear cell interactions are under the control of regulatory T cells [T suppressor (TS) cells] and it is speculated that the availability of these subsets may determine the magnitude of the late-phase response. Lymphokines and monokines which selectively activate neutrophils, eosinophils and monocytes include LIF, EAF and INF-gamma respectively. Macrophage-derived tumour necrosis factor (TNF) also amplifies the inflammatory response by its capacity to enhance eosinophil cytotoxicity. Eosinophil-derived agents such as PAF, LTC4, MBP and ECP might be responsible for submucosal oedema and non-specific bronchial hyperreactivity which are characteristic features of late-phase reactions. T cell-derived lymphokines such as EDF (IL-5), together with GM-CSF, might lead to eosinophilopoiesis and account for the prolonged eosinophilia of ongoing chronic asthma. The T cell is prominent in the pathology of chronic asthma and is possibly "chronically activated". Thus lymphocytes, driven by as yet undetermined "antigens" (possibly viral), may perpetuate the inflammatory response in and around the bronchi. IL-5-like products from these putative activated lymphocytes might perpetuate (a) eosinophil production by the bone marrow, (b) its release into the circulation, (c) its migration into bronchial tissue and (d) activation to release PAF, LTC4, MBP, etc.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Leucocytes in asthma. 306 26

The role of the eosinophilic granulocyte in immediate hypersensitivity reactions is generally believed to be a beneficial one since this cell may phagocytose mast cell granules and inactivate certain mast cell mediators. However it has become clear that the eosinophilic granulocyte also has potent secretory capacities, and by this property may contribute in a detrimental way to the allergic process. In studying the late phase allergen induced bronchoconstriction by means of bronchoalveolar lavage (BAL) an evident infiltration of eosinophilic granulocytes in the bronchioli in the beginning of the late phase asthmatic reaction was noticed. Since also eosinophil cationic protein (ECP) has been reported to be elevated in the lavage fluid an active secretory role of the eosinophil in the late phase asthmatic reaction seemed likely. Although the release of ECP and other granular proteins may contribute to epithelial damage and inflammation and thereby to an increase in bronchial hyperreactivity they do not explain the late phase bronchoconstrictive reaction. Since leukotrienes were thought possible candidates to cause this reaction it was decided to isolate eosinophils from human peripheral blood and to study their leukotriene synthesis pattern. To our surprise purified human eosinophils almost exclusively synthesize the strongly bronchoconstrictive leukotriene LTC4 in considerable quantities upon in vitro stimulation with either the calcium-ionophore A23187 or opsonized zymosan. These findings suggest that the eosinophil may play an active role in causing the late phase asthmatic reaction.
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PMID:The eosinophilic granulocyte an active participant in the late phase asthmatic reaction? 308 93

Although a great deal has been learned about the mediators produced by mast cells, the ultimate biologic function(s) of mast cell remains a mystery. Histamine, LTC4, PAF, and possibly tryptase (C3a generation) all enhance vasopermeability. Mediators with anticoagulant activities such as heparin and tryptase (fibrinogenolysis) and antithrombotic activity, PGD2, would appear to facilitate dispersion in tissues of the plasma ultrafiltrate brought there by the subgroup of mediators that enhance vasopermeability. In contrast, PAF causes platelet aggregation and chymase may cause arteriolar vasoconstriction (decreasing the volume of plasma reaching venules) by generation of angiotensin II. Assessment of any differential production of mediators by different types of mast cells will be of obvious importance in sorting out the physiologic responses to mast cell activation as well as the pathophysiology of allergic reactions.
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PMID:Mediators of human mast cells and human mast cell subsets. 310 66


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