Dahlén S E, Hansson G, Hedqvist P, Björck T, Granström E, Dahlén B
Proc Natl Acad Sci U S A. 1983 Mar;80(6):1712-6. doi: 10.1073/pnas.80.6.1712.
The leukotrienes C4, D4, and E4, previously referred to as slow reacting substance of anaphylaxis, elicited long-lasting contractions of bronchi isolated from two birch pollen-sensitive asthmatics. The leukotrienes were 1,000 times more potent on a molar basis than was histamine or prostaglandin F2 alpha. Moreover, 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 or 14C-labeled arachidonic acid, 15-hydroxyicosatetraenoic 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. However, cyclooxygenase inhibition with indomethacin had no effect on the contraction response to antigen in the bronchi, whereas, in the presence of U-60257, an inhibitor of leukotriene biosynthesis, the allergen neither released leukotrienes from the lung nor caused bronchial contraction. These findings indicate that leukotrienes C4, D4, and E4 are major mediators of allergic bronchoconstriction in man.
白三烯C4、D4和E4，以前被称为过敏反应迟缓反应物质，可引起从两名桦树花粉敏感哮喘患者分离出的支气管的持久收缩。白三烯在摩尔基础上的效力比组胺或前列腺素F2α强1000倍。此外，变应原从哮喘患者的肺组织中释放出白三烯C4、D4和E4，其数量似乎与过敏性支气管收缩密切相关。无论肺是用特异性变应原、离子载体A23187还是14C标记的花生四烯酸刺激，15-羟基二十碳四烯酸和其他脂氧合酶衍生的单羟基酸都是肺中花生四烯酸的主要代谢产物，血栓素A2和前列腺素I2是鉴定出的主要环氧化酶产物。然而，用吲哚美辛抑制环氧化酶对支气管对抗原的收缩反应没有影响，而在白三烯生物合成抑制剂U-60257存在的情况下，变应原既不从肺中释放白三烯，也不引起支气管收缩。这些发现表明白三烯C4、D4和E4是人类过敏性支气管收缩的主要介质。
