Role of cytosolic phospholipase A(2) in allergic response and parturition
Role of cytosolic phospholipase A(2) in allergic response and parturition
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DOI：
10.1038/37622
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发表时间：
1997-12-11
期刊：
影响因子：
64.8
通讯作者：
Shimizu, T
中科院分区：
文献类型：
--
作者：
Uozumi, N;Kume, K;Shimizu, T
磷脂酶A（2）（PLA（2））包括水解磷脂在sn-2位（1-3）的酯键的酶超家族。在该超家族的成员中，胞质PLA（2）引起了人们的注意，因为它优先水解花生四烯酸磷脂，并被亚微摩尔浓度的Ca 2+离子和促分裂原活化蛋白激酶（MAP激酶）磷酸化活化（4-8）。在这里，我们研究的功能，胞质PLA（2）在体内通过使用同源重组，以产生小鼠缺乏这种酶。这些小鼠在腹腔巨噬细胞中的类花生酸和血小板活化因子的产生显着减少。他们的卵清蛋白诱导的过敏反应显着减少，因为是他们的支气管反应乙酰甲胆碱。雌性突变小鼠未能分娩后代，但这些后代可以通过在足月时向母亲施用孕酮受体拮抗剂来挽救。与以前的发现（9-15）一起考虑，我们的结果表明，胞质PLA（2）在过敏反应和生殖生理学中起着非冗余的作用。
Phospholipase A(2) (PLA(2)) comprises a superfamily of enzymes that hydrolyse the ester bond of phospholipids at the sn-2 position(1-3). Among the members of this superfamily, cytosolic PLA(2) has attracted attention because it preferentially hydrolyses arachidonoyl phospholipids and is activated by submicromolar concentrations of Ca2+ ions and by phosphorylation by mitogen-activated protein kinases (MAP kinases)(4-8). Here we investigate the function of cytosolic PLA(2) in vivo by using homologous recombination to generate mice deficient in this enzyme. These mice showed a marked decrease in their production of eicosanoids and platelet-activating factor in peritoneal macrophages. Their ovalbumin-induced anaphylactic responses were significantly reduced, as was their bronchial reactivity to methacholine. Female mutant mice failed to deliver offspring, but these could be rescued by administration of a progesterone-receptor antagonist to the mother at term. Considered together with previous findings(9-15), our results indicate that cytosolic PLA(2) plays a non-redundant role in allergic responses and reproductive physiology.