Allergen challenge of lung tissue from asthmatics elicits bronchial contraction that correlates with the release of leukotrienes C4, D4, and E4.

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Abstract
The leukotrienes C4, D4 and E4, previously referred to as slow reacting substance of anaphylaxis, elicited long-lasting contractions of bronchi isolated from 2 birch pollen-sensitive asthmatics. The leukotrienes were 1000 times more potent on a molar basis than was histamine or prostaglandin F2.alpha.. Allergen released leukotrienes C4, D4, and E4 from the lung tissue of the asthmatics in amounts that appeared to correlate well to the anaphylactic bronchial contraction. Irrespectively of whether the lung was stimulated with specific allergen, the ionophore A23187 [calcimycin] or 14C-labeled arachidonic acid, 15-hydroxyeicosatetraenoic acid, and other lipoxygenase-derived monohydroxy acids were the major metabolites of arachidonic acid in the lung, and thromboxane A2 and prostaglandin I2 were the predominant cyclooxygenase products identified. Cyclooxygenase inhibition with indomethacin had no effect on the contraction response to antigen in the bronchi, whereas, in the presence of U-60257 [6,9-deepoxy-6,9-(phenylamine)-.DELTA.-6,8-prostaglandin I], an inhibitor of leukotriene biosynthesis, the allergen neither released leukotrienes from the lung nor caused bronchial contraction. These leukotrienes C4, D4 and E4 are apparently major mediators of allergic bronchoconstriction in man.
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