Lipid profiling reveals glycerophospholipid remodeling in zymosan-stimulated macrophages
Lipid profiling reveals glycerophospholipid remodeling in zymosan-stimulated macrophages
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DOI：
10.1021/bi0621617
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发表时间：
2007-05-22
期刊：
影响因子：
2.9
通讯作者：
Marnett, Lawrence J.
中科院分区：
文献类型：
--
作者：
Rouzer, Carol A.;Ivanova, Pavlina T.;Marnett, Lawrence J.
通过质谱仪进行的全面的脂谱分析提供了每个主要类别中各个甘油磷脂的相对分布的比较数据。应用该方法分析酵母多糖吞噬过程中小鼠原代滞留腹膜巨噬细胞(RPM)的甘油磷脂重塑，发现每一种主要的花生四烯酸(20：4)磷脂酰胆碱(GPCho)以及部分20：4磷脂酰肌醇(GPIns)和磷脂酰甘油(GPGro)的水平显著降低。含有20：4磷脂酰乙醇胺(GPEtn)的物种没有检测到净变化。用脂多糖预处理RPM后，反应的幅度和动力学发生了细微的变化，但对酵母多糖诱导的甘油磷脂重塑的总体模式没有影响。用吲哚美辛抑制前列腺素(PG)的合成降低了含有20：4的二酰基的变化幅度，但不能降低烷基酰基的变化幅度。阻断与硫柳汞的20：4反应对酵母多糖引起的GPCho、GPIns或GPGro物种的变化幅度没有影响，但显示烷基酰基Getn物种的水平下降。RAW264.7细胞含有比RPM低得多的磷脂20：4，对酵母多糖的反应合成PG较差。用粒细胞-巨噬细胞集落刺激因子、脂多糖和干扰素-γ预处理可显著增加这些细胞的20：4动员和PG合成的程度。然而，在最大的酵母多糖依赖的PG合成条件下，唯一表现出显著变化的甘油磷脂是含有20：4的质膜基GPEtn。这些结果表明，在酵母多糖刺激的RPM中，GPCHo是20：4动员的主要最终来源，但20：4动员可能涉及烷基酰基GPEtn物种的中间转化。
Comprehensive lipid profiling by mass spectrometry provides comparative data on the relative distribution of individual glycerophospholipids within each of the major classes. Application of this method to the analysis of glycerophospholipid remodeling in murine primary resident peritoneal macrophages (RPMs) during zymosan phagocytosis reveals significant decreases in the levels of every major arachidonic acid (20:4)-containing species of phosphatidylcholine (GPCho) and in selected 20:4-containing phosphatidylinositol (GPIns) and phosphatidylglycerol (GPGro) species. No net changes in 20:4-containing phosphatidylethanolamine (GPEtn) species were detected. Pretreatment of RPMs with LPS resulted in subtle changes in the magnitude and kinetics of the response but had no effect on the overall pattern of zymosan-induced glycerophospholipid remodeling. Inhibition of prostaglandin (PG) synthesis with indomethacin reduced the magnitude of the changes in 20:4-containing diacyl but not alkyl acyl species. Blockade of 20:4 reacylation with thimerosal had no effect on the magnitude of the zymosan-induced changes in GPCho, GPIns, or GPGro species but revealed decreases in the level of alkyl acyl GEtn species. RAW264.7 cells contain much lower levels of phospholipid 20:4 than do RPMs and synthesize PGs poorly in response to zymosan. Pretreatment with granulocyte-macrophage colony stimulating factor, lipopolysaccharide, and interferon-gamma substantially increased the extent of 20:4 mobilization and PG synthesis in these cells. However, under conditions of maximal zymosan-dependent PG synthesis, the only glycerophospholipid that exhibited a significant change was a 20:4-containing plasmenyl GPEtn. These results suggest that GPCho is the major ultimate source of 20:4 that is mobilized in zymosan-stimulated RPMs but that 20:4 mobilization may involve the intermediate turnover of alkyl acyl GPEtn species.