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)

1. The time course of mediator release and the hypothesis that the ratio of eicosanoids to histamine might alter with the intensity of stimulus or its route of administration has been explored in isolated perfused lung from sensitized guinea-pigs challenged with ovalbumin. 2. Histamine and prostaglandin release was rapid in onset and virtually complete within 10 min. Thromboxane B2 (TXB2) and leukotriene D4 (LTD4) release, however, was more sustained. Release of the major prostanoid metabolites was relatively delayed compared to that of the parent compounds and was more sustained. 3. Mediator release was antigen-dose dependent and TXB2, prostaglandin D2 (PGD2) and LTD4 release linearly related to histamine concentrations (P less than 0.05). However, the ratio of the percentage maximum release of eicosanoids relative to histamine was greatest with low doses of ovalbumin. 4. At a low antigen dose (10 micrograms ovalbumin), histamine and prostanoid release was greatest when the challenge was via the airway rather than into the pulmonary artery and the greatest differences were in PGF2 alpha levels. At near maximal challenge (1 mg ovalbumin) there was little difference in concentrations of PGD2, TXB2, 6-oxo-PGF1 alpha and LTD4 by either route, but PGF2 alpha levels remained greater. 5. The results indicate that biologically active amounts of prostanoids may be released from sensitized lung at low degrees of mast cell activation and that differences in mediator release following antigen administration to the airway or into the pulmonary vasculature simply reflects its accessibility to sensitized cells.
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PMID:Release of arachidonic acid metabolites and histamine from sensitized guinea-pig lung following antigen challenge. 245 78

Antigen challenge of passively sensitized chopped human lung resulted in the generation of several arachidonic acid cyclooxygenase metabolites (AACM): thromboxane A2 (TxA2) as measured by its stable metabolite TxB2, prostaglandin D2 (PgD2), prostacyclin (PgI2) as measured by its stable metabolite 6-keto-PgF1 alpha, prostaglandin F2 alpha (PgF2 alpha), and prostaglandin E (PgE). The kinetics of AACM release after antigen challenge paralleled histamine release. All AACM were released in an antigen dose-dependent manner and reached maximal release at antigen concentrations lower than those required for maximal histamine release. Quantitatively, of the AACM measured, PgD2 and PgI2 were found to predominate in anaphylactic reactions of human lung parenchyma. Generation of PgD2 and PgI2 were 3- to 7-fold greater than that of other AACM measured. Thromboxane B2 was generated in quantities comparable to PgE and PgF2 alpha. Studies were designed to test the hypothesis that lung smooth muscle contraction per se can account for the generated AACM that are released during anaphylaxis of the lung. The studies compared antigen-induced AACM generation with methacholine-induced (10(-4) M) AACM generation. The failure to confirm this hypothesis was especially evident for PgD2 where release was dependent on mast cell activation. Thromboxane A2, PgD2, and PgI2 have been reported to have potent effects on smooth muscle. Our data suggested that these AACM are generated in such sufficient quantities that they may function in important aspects of the modulation of hypersensitivity responses in human lungs.
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PMID:Anaphylactic release of thromboxane A2, prostaglandin D2, and prostacyclin from human lung parenchyma. 617 Feb 42

Cardiac immediate hypersensitivity reactions in vitro are characterized by tachycardia, arrhythmias and coronary constriction. Whereas endogenous cardiac histamine release is responsible for the generation of arrhythmias, metabolites of arachidonic acid mediate the fall in coronary flow. In the present study, we have shown that antigenic challenge of sensitized guinea-pig hearts results in the release into the coronary effluent of immunoreactive thromboxane B2, 6-keto prostaglandin (PG) F1 alpha and PGF2 alpha. Thromboxane B2 was the predominant metabolite generated. After the administration of histamine (1-100 micrograms) or a partially purified preparation of slow-reacting substance of anaphylaxis (5-100 U) to the sensitized heart there was no detectable release of thromboxane B2 into the coronary effluent. After the administration of sodium arachidonate (3 X 10(-6) M) to the sensitized heart 40 min after antigenic challenge, there was a predominant release of 6-keto PGF1 alpha into the coronary effluent. Pretreatment of sensitized hearts with aspirin (5.5 X 10(-5) M), indomethacin (1.4 X 10(-5) M) or 1-(2-isopropylphenyl)imidazole (5.4 X 10(-5) M) resulted in inhibition of antigen-induced thromboxane B2 release and coronary vasoconstriction. These results suggest that during immediate hypersensitivity reactions, the coronary vasculature may be predisposed to ischemic and thrombotic episodes as a result of thromboxane release. Thromboxane formation occurs independently of the actions of histamine and slow-reacting substance of anaphylaxis and, since it is not generated preferentially by the coronary circulation of the sensitized heart in response to arachidonate infusion, it is plausible to suggest that it is of mast cell origin.
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PMID:Thromboxane and prostacyclin release during cardiac immediate hypersensitivity reactions in vitro. 689 66

The role of mast cells in pulmonary artery occlusion/reperfusion injury was examined. Lung tissue was obtained from dogs after left pulmonary artery occlusion for 48 h (n = 5) or after similar occlusion followed by 4 h of reperfusion (n = 11). By light microscopy and morphometry, the percentage of mast cells increased 2.4-fold (p < 0.05) in nonoccluded right lungs and 2.9-fold (p < 0.05) in occluded left lungs without reperfusion compared with that in control lungs. After reperfusion, the occluded left lung contained 1.8-fold (p < 0.05) as many mast cells as the nonoccluded right lung and 4.2-fold (p < 0.05) more than that in control lungs. Hydroxyurea did not significantly affect the number of mast cells observed in the right and left lungs after ischemia/reperfusion; 39.8% and 54.4% of the mast cells were degranulated in nonoccluded right lung and occluded left lung preparations, respectively, after left pulmonary artery ischemia/reperfusion (each, p < 0.05 compared with control lungs). The release of eicosanoids into the airways during ischemia/reperfusion injury was also examined. Thromboxane B2 and leukotriene B4 were markedly increased (each, p < 0.05 compared with that in control lungs) in bronchial lavage fluids from both nonoccluded and occluded lungs compared with sham-occluded lungs. Thus, mast cell recruitment and degranulation may play a role in lung ischemia/reperfusion injury.
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PMID:Lung mast cells increase in number and degranulate during pulmonary artery occlusion/reperfusion injury in dogs. 838 32