Schulam P G, Kuruvilla A, Putcha G, Mangus L, Franklin-Johnson J, Shearer W T
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.
J Immunol. 1991 Mar 1;146(5):1642-8.
Platelet-activating factor is a potent mediator of the inflammatory response. Studies of the actions of platelet-activating factor have centered mainly around neutrophils, monocytes, and platelets. In this report we begin to uncover the influence of platelet-activating factor on B lymphocytes. Employing the EBV-transformed human B cell line SKW6.4, we demonstrate that platelet-activating factor significantly alters membrane phospholipid metabolism indicated by the incorporation of 32P into phosphatidylcholine, phosphatidylinositol, and phosphatidic acid but not significantly into phosphatidylethanolamine at concentrations ranging from 10(-9) to 10(-6) M. The inactive precursor, lyso-platelet-activating factor, at a concentration as high as 10(-7) M had no effect on any of the membrane phospholipids. We also show that platelet-activating factor from 10(-12) to 10(-6) M induced rapid and significant elevation in intracellular calcium levels, whereas lyso-platelet-activating factor was again ineffective. We further demonstrate the impact of platelet-activating factor binding to B cells by measuring platelet-activating factor induced arachidonic acid release and 5-hydroxyeicosatetraenoic acid production. Moreover, platelet-activating factor was capable of inducing transcription of the nuclear proto-oncogenes c-fos and c-jun. Finally we explored the possible role of 5-hydroxyeicosatetraenoic acid as a regulator of arachidonic acid liberation demonstrating that endogenous 5-lipoxygenase activity modulates platelet-activating factor induced arachidonic acid release perhaps acting at the level of phospholipase A2. In summary, platelet-activating factor is shown here to have a direct and profound effect on a pure B cell line.
血小板活化因子是炎症反应的一种强效介质。对血小板活化因子作用的研究主要集中在中性粒细胞、单核细胞和血小板上。在本报告中，我们开始揭示血小板活化因子对B淋巴细胞的影响。利用EB病毒转化的人B细胞系SKW6.4，我们证明，在浓度范围为10^(-9)至10^(-6) M时，血小板活化因子显著改变膜磷脂代谢，表现为32P掺入磷脂酰胆碱、磷脂酰肌醇和磷脂酸中，但对磷脂酰乙醇胺的掺入无显著影响。浓度高达10^(-7) M的无活性前体溶血血小板活化因子对任何膜磷脂均无影响。我们还表明，浓度为10^(-12)至10^(-6) M的血小板活化因子可诱导细胞内钙水平迅速且显著升高，而溶血血小板活化因子再次无效。我们通过测量血小板活化因子诱导的花生四烯酸释放和5-羟基二十碳四烯酸生成，进一步证明了血小板活化因子与B细胞结合的影响。此外，血小板活化因子能够诱导核原癌基因c-fos和c-jun的转录。最后，我们探讨了5-羟基二十碳四烯酸作为花生四烯酸释放调节剂的可能作用，证明内源性5-脂氧合酶活性可能在磷脂酶A2水平上调节血小板活化因子诱导的花生四烯酸释放。总之，本文表明血小板活化因子对一个纯B细胞系有直接而深远的影响。
