Robinson B S, Hii C S, Poulos A, Ferrante A
Department of Immunology, Women's and Children's Hospital, North Adelaide, Australia.
J Lipid Res. 1996 Jun;37(6):1234-45.
Although tumor necrosis factor-alpha (TNF-alpha) has been shown to induce marked changes in the physiology/pathophysiology of cells, little is known about the effects of this cytokine on cellular lipid metabolism. In this study we examined the effects of TNF-alpha on the metabolism of eicosatetraenoic acid (arachidonic acid, (20:4(n-6)) in human neutrophils. Pretreatment of neutrophils with TNF-alpha caused a rapid increase in the incorporation of [1-14C]20:4(n-6) substrate into cellular phosphatidylinositol and phosphatidic acid and a slower rise in the incorporation into phosphatidylcholine and phosphatidylethanolamine. Radioactivity was exclusively associated with the sn-2 position of each molecule. The labeling pattern of other phospholipids, neutral lipids, and eicosanoids was unchanged. TNF-alpha had no effect on the distribution of radioactivity in 1-acyl, 1-alkyl, and 1-alk-1-enyl subclasses of phosphatidylcholine, phosphatidylethanolamine, and triglyceride. Chain elongation, beta-oxidation and desaturation of [1-14C]20:4(n-6) were not modulated by the cytokine. TNF-alpha stimulated the release of [3H]20:4(n-6) from prelabeled neutrophils and also induced the production of endogenous unesterified 20:4(n-6). Concomitantly, treatment with the cytokine caused a decrease in the mass of cellular phosphatidylinositol, phosphatidylcholine, and phosphatidylethanolamine and an increase in the levels of corresponding lysophospholipids, but had no significant effect on sphingomyelin, phosphatidic acid, diglyceride, and other lipids. TNF-alpha did not evoke neutrophils prelabeled with [3H]lyso platelet activating factor to produce [3H]phosphatidylethanol, [3H]phosphatidic acid, or [3H]diglyceride in the presence of ethanol, indicating that phospholipases D and C were not activated. Treatment of the leukocytes with the cytokine had no effect on the activity of neutral and acidic sphingomyelinase. These data collectively provide evidence that TNF-alpha specifically induces the turnover of neutrophil phosphatidylinositol, phosphatidylcholine and phosphatidylethanolamine, which are enriched with 20:4(n-6) by the activation of phospholipase A2.
尽管肿瘤坏死因子-α（TNF-α）已被证明可诱导细胞生理/病理生理学发生显著变化，但关于这种细胞因子对细胞脂质代谢的影响却知之甚少。在本研究中，我们检测了TNF-α对人中性粒细胞中二十碳四烯酸（花生四烯酸，(20:4(n-6))）代谢的影响。用TNF-α预处理中性粒细胞导致[1-14C]20:4(n-6)底物掺入细胞磷脂酰肌醇和磷脂酸的量迅速增加，而掺入磷脂酰胆碱和磷脂酰乙醇胺的量增加较慢。放射性仅与每个分子的sn-2位相关。其他磷脂、中性脂质和类花生酸的标记模式未发生变化。TNF-α对磷脂酰胆碱、磷脂酰乙醇胺和甘油三酯的1-酰基、1-烷基和1-烯基-1-烯基亚类中的放射性分布没有影响。[1-14C]20:4(n-6)的链延长、β-氧化和去饱和不受该细胞因子的调节。TNF-α刺激预先标记的中性粒细胞释放[3H]20:4(n-6)，并诱导内源性未酯化的20:4(n-6)的产生。同时，用该细胞因子处理导致细胞磷脂酰肌醇、磷脂酰胆碱和磷脂酰乙醇胺的质量减少，相应溶血磷脂的水平增加，但对鞘磷脂、磷脂酸、甘油二酯和其他脂质没有显著影响。在乙醇存在的情况下，TNF-α不会促使预先用[3H]溶血血小板活化因子标记的中性粒细胞产生[3H]磷脂酰乙醇、[3H]磷脂酸或[3H]甘油二酯，这表明磷脂酶D和C未被激活。用该细胞因子处理白细胞对中性和酸性鞘磷脂酶的活性没有影响。这些数据共同提供了证据，表明TNF-α通过激活磷脂酶A2特异性诱导富含20:4(n-6)的中性粒细胞磷脂酰肌醇、磷脂酰胆碱和磷脂酰乙醇胺的周转。
