Inflammatory platelet-activating factor-like phospholipids in oxidized low density lipoproteins are fragmented alkyl phosphatidylcholines

作     者：Marathe, GK Davies, SS Harrison, KA Silva, AR Murphy, RC Castro-Faria-Neto, H Prescott, SM Zimmerman, GA McIntyre, TM 

作者机构：Univ Utah Dept Pathol Salt Lake City UT 84112 USA Univ Utah Dept Internal Med Salt Lake City UT 84112 USA Univ Utah Huntsman Canc Inst Salt Lake City UT 84112 USA Natl Jewish Med & Res Ctr Dept Pediat Denver CO 80206 USA Fiocruz MS Dept Fisiol & Farmacodinam IOC BR-21045900 Rio De Janeiro Brazil 

出 版 物：《JOURNAL OF BIOLOGICAL CHEMISTRY》 (生物化学杂志)

年 卷 期：1999年第274卷第40期

页      面：28395-28404页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

基　　金：National Heart, Lung, and Blood Institute, NHLBI, (R01HL044513) National Heart, Lung, and Blood Institute, NHLBI 

主　　题：色谱法 高压液相 炎症介导素类/化学 炎症介导素类/代谢 脂蛋白类 LDL/代谢 质谱分析法 氧化还原 磷脂酰胆碱类/化学 磷脂酰胆碱类/代谢 血小板活化因子/化学 血小板活化因子/代谢 重组蛋白质类/化学 重组蛋白质类/代谢 人类 

摘      要：Oxidation of human low density lipoprotein (LDL) generates proinflammatory mediators and underlies early events in atherogenesis. We identified mediators in oxidized LDL that induced an inflammatory reaction in vivo, and activated polymorphonuclear leukocytes and cells ectopically expressing human platelet-activating factor (PAF) receptors, Oxidation of a synthetic phosphatidylcholine showed that an sn-l ether bond confers an 800-fold increase in potency. This suggests that rare ether-linked phospholipids in LDL are the likely source of PAF-like activity in oxidized LDL, Accordingly, treatment of oxidized LDL with phospholipase A, greatly reduced phospholipid mass, but did not decrease its PAF-like activity. Tandem mass spectrometry identified traces of PAF, and more abundant levels of 1-O-hexadecyl-2-(butanoyl or butenoyl)-sn-glycero-3-phosphocholines (C-4-PAF analogs) in oxidized LDL that comigrated with PAF-like activity. Synthesis showed that either C-4-PAF was just 10-fold less potent than PAF as a PAF receptor ligand and agonist. Quantitation by gas chromatography-mass spectrometry of pentafluorobenzoyl derivatives shows the C-4-PAF analogs were 100-fold more abundant in oxidized LDL than PAF, Oxidation of synthetic alkyl arachidonoyl phosphatidylcholine generated these C-4-PAFs in abundance. These results show that quite minor constituents of the LDL phosphatidylcholine pool are the exclusive precursors for PAF-like bioactivity in oxidized LDL.