Anaphylactic release of thromboxane A2, prostaglandin D2, and prostacyclin from human lung parenchyma.
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.
D000707:Anaphylaxis / Q000378:metabolism*; D000941:Antigens; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D015237:Dinoprost; D011464:Epoprostenol / Q000096:biosynthesis*; D006636:Histamine Release; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology; D008688:Methacholine Compounds; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000276:immunology / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D011457:Prostaglandins D / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D000941:Antigens; D001095:Arachidonic Acids; D008688:Methacholine Compounds; D011453:Prostaglandins; D011457:Prostaglandins D; D011458:Prostaglandins E; D011460:Prostaglandins F; D013931:Thromboxanes; D016718:Arachidonic Acid; D013928:Thromboxane A2; D015237:Dinoprost; D011464:Epoprostenol