Role of group V phospholipase A2 in zymosan-induced eicosanoid generation and vascular permeability revealed by targeted gene disruption
Role of group V phospholipase A2 in zymosan-induced eicosanoid generation and vascular permeability revealed by targeted gene disruption
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DOI：
10.1074/jbc.m313748200
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发表时间：
2004-04-16
影响因子：
4.8
通讯作者：
Arm, JP
中科院分区：
文献类型：
--
作者：
Satake, Y;Diaz, BL;Arm, JP
关于低分子量分泌型磷脂酶 A(2) (sPLA(2)) 酶在类二十烷酸生成中的贡献的结论依赖于从转染细胞获得的数据或无法区分哺乳动物 sPLA(2) 酶大家族各个成员的抑制剂的使用。为了阐明 V 组 sPLA(2) 的作用，我们使用靶向基因破坏来产生缺乏这种酶的小鼠。与来自野生型同窝小鼠的巨噬细胞相比，来自V组sPLA(2)缺失小鼠的腹膜巨噬细胞中酵母聚糖诱导的白三烯C-4和前列腺素E-2的产生减弱了50%。此外，与野生型对照相比，V组sPLA(2)缺失小鼠中腹膜内注射酵母聚糖引起的血浆渗出的早期阶段以及伴随的半胱氨酰白三烯的体内生成显着减弱。这些数据提供了明确的证据，表明 V 族 sPLA(2) 在调节类二十烷酸生成以响应体外和体内免疫反应的急性先天刺激中的作用，表明该酶在先天免疫中的作用。
Conclusions regarding the contribution of low molecular weight secretory phospholipase A(2) (sPLA(2)) enzymes in eicosanoid generation have relied on data obtained from transfected cells or the use of inhibitors that fail to discriminate between individual members of the large family of mammalian sPLA(2) enzymes. To elucidate the role of group V sPLA(2), we used targeted gene disruption to generate mice lacking this enzyme. Zymosan-induced generation of leukotriene C-4 and prostaglandin E-2 was attenuated similar to50% in peritoneal macrophages from group V sPLA(2)-null mice compared with macrophages from wild-type littermates. Furthermore, the early phase of plasma exudation in response to intraperitoneal injection of zymosan and the accompanying in vivo generation of cysteinyl leukotrienes were markedly attenuated in group V sPLA(2)-null mice compared with wild-type controls. These data provide clear evidence of a role for group V sPLA(2) in regulating eicosanoid generation in response to an acute innate stimulus of the immune response both in vitro and in vivo, suggesting a role for this enzyme in innate immunity.