Uozumi N, Kume K, Nagase T, Nakatani N, Ishii S, Tashiro F, Komagata Y, Maki K, Ikuta K, Ouchi Y, Miyazaki J, Shimizu T
Department of Biochemistry, University of Tokyo, Japan.
Nature. 1997 Dec 11;390(6660):618-22. doi: 10.1038/37622.
Phospholipase A2 (PLA2) comprises a superfamily of enzymes that hydrolyse the ester bond of phospholipids at the sn-2 position. Among the members of this superfamily, cytosolic PLA2 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). Here we investigate the function of cytosolic PLA2 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, our results indicate that cytosolic PLA2 plays a non-redundant role in allergic responses and reproductive physiology.
磷脂酶A2（PLA2）是一个酶的超家族，可水解磷脂在sn-2位的酯键。在这个超家族的成员中，胞质型磷脂酶A2引起了人们的关注，因为它优先水解花生四烯酰磷脂，并被亚微摩尔浓度的钙离子以及丝裂原活化蛋白激酶（MAP激酶）磷酸化激活。在这里，我们通过同源重组来生成缺乏这种酶的小鼠，从而在体内研究胞质型磷脂酶A2的功能。这些小鼠腹膜巨噬细胞中类花生酸和血小板活化因子的产生显著减少。它们由卵清蛋白诱导的过敏反应明显降低，对乙酰甲胆碱的支气管反应性也是如此。雌性突变小鼠无法产仔，但在足月时给母体施用孕酮受体拮抗剂可使其得到挽救。结合先前的研究结果，我们的结果表明胞质型磷脂酶A2在过敏反应和生殖生理学中发挥着不可替代的作用。
