Phospholipase D is involved in cytosolic phospholipase A2‐dependent selective release of arachidonic acid by fMLP‐stimulated rat neutrophils

FEBS Letters

Amemiya, Kouji¹  Murakami, Makoto²  Fujita, Ken-ichi¹  Yamashita, Fumio¹  Kudo, Ichiro² 

[1] Department of Biological Science, Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., Gensuke, 301, Fujieda-shi, Shizuoka 426, Japan;Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Hatanodai 1-5-8, Shinagawa-ku, Tokyo 142, Japan

关键词: Phospholipase A2;    Phospholipase D;    Neutrophil;    Formyl-Met-Leu-Phe;    Arachidonic acid;    Rat;    cPLA2;    cytosolic phospholipase A2;    PLD;    phospholipase D;    fMLP;    N-formyl-Met-Leu-Phe;    PMN;    polymorphonuclear neutrophils;    AACOCF3;    arachidonyl trifluoromethyl ketone;    PA;    phosphatidic acid;    PEt;    phosphatidylethanol;    PC;    phosphatidylcholine;    pBPB;    4-bromophenacylbromide;    DG;    diacylglycerol;    MAP kinase;    mitogen-activated protein kinase;    HBSS;    Hanks' balanced salt solution;    1-BODIPY-PC;    2-decanoyl-1-(O-(11-(4;    4-difluoro-5;    7-dimethyl-4-bora-3a;    4a-diaza-S-indacene-3-propionyl)amino)undecyl)-sn-glycero-3-phosphocholine;   

DOI  :  10.1016/0014-5793(96)01056-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

When rat polymorphonuclear neutrophils (PMN) were treated with N-formyl-Met-Leu-Phe (fMLP), the release of arachidonic acid in preference to other fatty acids was observed. Levels of arachidonic acid reached a plateau within 5 min, and were accompanied by an ∼ 4-fold increase in in vitro phospholipase (PL) A₂ and PLD activities in PMN lysates. Treatment of PMN with ethanol (an inhibitor of PLD-mediated phosphatidic acid formation), propranolol (a phosphatidic acid phosphatase inhibitor), or 4-bromophenacylbromide (a PLA₂ inhibitor), each suppressed fMLP-stimulated arachidonate release. Treatment with RHC-80267 (a diacylglycerol lipase inhibitor), however, had no such effect. The cytosolic PLA₂ (cPLA₂) inhibitor, arachidonoyl trifluoromethyl ketone, suppressed PLA₂ activity in PMN homogenates and arachidonate release by fMLP-treated PMN. These results suggest that fMLP-elicited arachidonate release is mediated by cPLA₂ but not diacylglycerol lipase, and that the activation of cPLA₂ is downstream of the PLD-dependent signaling pathway.

【 授权许可】

Unknown