SLOW-REACTING SUBSTANCES, LEUKOTRIENE-C4 AND LEUKOTRIENE-D4, INCREASE THE RELEASE OF MUCUS FROM HUMAN AIRWAYS INVITRO

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Abstract
Allergic pulmonary reactions in vivo lead to airway constriction and mucous secretion, whereas in vitro lung anaphylaxis leads to mediator release and increased mucus glycoprotein secretion from cultured human airways. Using quantitation of radiolabeled mucus glucoprotein from cultured airways as a model for mucus release, the effects of 2 leukotrienes, LTC4 and LTD4, were assesed. Both biosynthetic and synthetic LTC4 and LTD4 produced dose-related increases in mucus production at concentrations of 1-1000 U/ml (20-20,000 pg [LTD4] and 24-24,000 pg [LTC4]/ml). These enhancing actions were seen in 11 of 11 lung cultures, and were significantly prevented by the specific SRS-A [slow-reacting substance of anaphylaxis] antagonist FPL 55712 [7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropoxy]4-oxo-8-propyl-4H-1-benzopyran-2-carboxylic acid monosodium salt]. LTC4 and LTD4, 2 major components of the allergic mediator SRS-A, are potent mucus secretagogues and may possibly contribute to the mucus secretion observed during allergic reactions in vitro and in vivo.