Huang Y H, Schäfer-Elinder L, Wu R, Claesson H E, Frostegård J
Department of Medicine, Division of Rheumatology, Karolinska Institute, Stockholm, Sweden.
Clin Exp Immunol. 1999 May;116(2):326-31. doi: 10.1046/j.1365-2249.1999.00871.x.
Oxidized low-density lipoprotein (oxLDL) consists of both lipid components and apoprotein B100. OxLDL has both proinflammatory and cytotoxic properties. The present study was undertaken to investigate the effects of components in the lipid moiety of oxLDL on immune activation as determined by cytokine and immunoglobulin secretion. LPC induced interferon-gamma (IFN-gamma) secretion in peripheral blood mononuclear leucocytes from healthy blood donors. The effect varied between individuals, and there were both responders and non-responders. Furthermore, LPC induced enhanced antibody production, indicating B cell activation. None of eight oxysterols, arachidonic acid (AA), or 15-lipoxygenase products of AA tested had immune stimulatory properties. We recently demonstrated that PAF and oxLDL induce IFN-gamma secretion by a common mechanism. LPC-induced IFN-gamma secretion was inhibited by a specific PAF receptor antagonist, WEB 2170, indicating that the PAF receptor is involved in LPC-induced immune activation. Both oxLDL- and LPC-induced antibody formation was inhibited by WEB 2170. Furthermore LPC also induced tumour necrosis factor-alpha secretion, and this effect was inhibited by WEB 2170. LPC is produced during lipid oxidation (as in oxLDL), but also by enzymes such as phospholipase A2. The findings indicate that LPC may play an important role in inflammatory reactions, including atherosclerosis.
氧化型低密度脂蛋白（oxLDL）由脂质成分和载脂蛋白B100组成。oxLDL具有促炎和细胞毒性特性。本研究旨在探讨oxLDL脂质部分的成分对免疫激活的影响，免疫激活通过细胞因子和免疫球蛋白分泌来确定。溶血磷脂酰胆碱（LPC）可诱导健康献血者外周血单个核白细胞分泌干扰素-γ（IFN-γ）。个体之间的效应存在差异，既有反应者也有无反应者。此外，LPC可诱导抗体产生增强，表明B细胞被激活。所检测的8种氧化甾醇、花生四烯酸（AA）或AA的15-脂氧合酶产物均无免疫刺激特性。我们最近证明，血小板活化因子（PAF）和oxLDL通过共同机制诱导IFN-γ分泌。LPC诱导的IFN-γ分泌受到特异性PAF受体拮抗剂WEB 2170的抑制，表明PAF受体参与了LPC诱导的免疫激活。WEB 2170可抑制oxLDL和LPC诱导的抗体形成。此外，LPC还可诱导肿瘤坏死因子-α分泌，且该效应受到WEB 2170的抑制。LPC在脂质氧化过程中（如在oxLDL中）产生，但也可由磷脂酶A2等酶产生。这些发现表明，LPC可能在包括动脉粥样硬化在内的炎症反应中起重要作用。
