Fluoride activates diradylglycerol and Superoxide generation in human neutrophils via PLD/PA phosphohydrolase‐dependent and ‐independent pathways

FEBS Letters

Olson, Susan C.¹  Lambeth, J.David¹  Tyagi, Shiv Raj¹ 

[1] Department of Biochemistry, Emory University Medical School, Atlanta, GA 30322, USA

关键词: Superoxide generation;    Diacylglycerol;    Diradylglycerol;    Phospholipase D;    Fluoride;    Neutrophil;    DAG;    1;    2-diacylglycerol;    EAG;    1-O-alkyl;    2-acylglycerol;    PA;    phosphatidic acid;    fMLP;    formyl-methionylleucyl-phenylalanine;    PI;    phosphatidylinositol;    ATP;    adenosine 5 '-triphosphate;    CB;    cytochalasin B;    PC;    phosphatidylcholine;    TLC;    thin-layer chromatography;    PBS;    phosphate-buffered saline;    PETH;    phosphatidylethanol;    EtOH;    ethanol;    GM-CSF;    granulocyte/monocyte colony-stimulating factor;    PMA;    phorbol 12-myristate 13-acetate;   

DOI  :  10.1016/0014-5793(90)80439-P

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In contrast to the rapid, ethanol-inhibited Superoxide generation by the receptor-linked agonist formyl-methionyl-leucyl-phenylalanine (fMLP), fluoride-activated Superoxide generation occurs after a prolonged lag, and as shown herein is relatively ethanol-insensitive. We have investigated fluoride-activation of diradylglycerol generation and phospholipase D activity. Fluoride induces a very large increase in diradylglycerol mass (both 1,2-diacylglycerol (DAG) and 1-O-alkyl,2-acylglycerol (EAG)), with kinetics similar to Superoxide generation. Unlike fMLP-activated diglyceride generation which is completely inhibited by ethanol, that produced by fluoride is only partially (30%) blocked. When the phosphatidylcholine pool is ³H-prelabeled, fluoride activates both [³H]phosphatidic acid (PA) and [³H]diglyceride generation with similar kinetics. Partial inhibition of the production of these species by ethanol was seen, coincident with the appearance of [³H]phosphatidylethanol, indicating phospholipase D-dependent transphosphatidylation had occurred. The data are consistent with the fluoride activation of PA and diglyceride generation by both phospholipase D-dependent and -independent (presumably phospholipase C) mechanisms.

【 授权许可】

Unknown