Leukotrienes and the Lung

Background: Feldberg & Kellaway [1] were the first to demonstrate the formation and release from envenomed dog and monkey lungs of a substance which caused a delayed and slow contraction of the guinea-pig jejunum; subsequently, Kellaway & Trethewie [2] described release of a slow-reacting substance (SRS) during acute anaphylaxis of the guinea-pig lung. Brocklehurst [3, 4] later reported the formation of an SRS, which he called slow-reacting substance of anaphylaxis (SRS-A), during anaphylaxis of guinea-pig, rabbit, monkey and human lungs. This substance had similar activity to SRS on guinea-pig ileum and was unaffected by the newly developed antihistamine, mepyramine. Release of SRS-A was demonstrated during antigen-induced constriction of bronchioles from subjects with asthma [5], suggesting that SRS-A might be of importance in the pathogenesis of human asthma [6, 7]. The development of techniques for the generation and partial purification of SRS-A from the rat peritoneal cavity [6] and intact guinea-pig lungs [8] permitted characterization of its biological properties.