Effects of dexamethasone on mediator release from human lung fragments and purified human lung mast cells.
Purified human lung mast cells released histamine, leukotrienes, prostaglandin (PG) D2, thromboxane B2 (TxB2), and PGF2 alpha in response to anti-IgE stimulation. Incubation of the cells for 24 h with 10(-6) M dexamethasone, a treatment that inhibits mediator release from human basophils, had no effect on the release of these mediators from mast cells. Dexamethasone treatment of human lung fragments led to little or no inhibition of anti-IgE-induced release of the mast cell-derived mediator, histamine, but produced a significant inhibition of the release of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha. As was the case with purified mast cells, the steroid did not inhibit the release of PGD2 or TxB2 from human lung fragments. Comparison of the quantities of PGD2 and TxB2 produced by purified cells and human lung fragments reveals that the mast cells produce quantities of these metabolites sufficient to account for the entire amount produced by challenged lung fragments. Dexamethasone inhibited spontaneous release from lung fragments of all cyclooxygenase products measured. These results suggest that the human lung parenchymal mast cell phospholipase is not inhibited by dexamethasone, whereas other phospholipase(s) in the lung are inhibited by the steroid. These results may be useful in explaining the resistance of acute allergic reactions, including anaphylaxis, to steroids, despite the potent antiinflammatory activity of steroids on subacute and chronic inflammation, such as in bronchial asthma, which may be initiated by IgE-dependent mechanisms.
D012898:Autacoids / Q000378:metabolism*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D015237:Dinoprost; D006632:Histamine / Q000378:metabolism; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007073:Immunoglobulin E / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D013189:SRS-A / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism
D012898:Autacoids; D007106:Immune Sera; D011457:Prostaglandins D; D011460:Prostaglandins F; D013189:SRS-A; D007073:Immunoglobulin E; D013929:Thromboxane B2; D003907:Dexamethasone; D006632:Histamine; D015237:Dinoprost; D015230:Prostaglandin D2