Role of phospholipid molecular species containing poly unsaturated fatty acids

我们认为，几种来源于肌醇脂类的纳米分子血栓素A_2(TXA_2)在胶原激活的过程中可能直接引起人血小板内钙离子的动员。花生四烯酸代谢产物血栓素B_2与磷脂酸的形成是平行的，没有形成溶血磷脂酸或溶血磷脂酰肌醇，这表明在胞内低钙浓度下，花生四烯酸是通过PI专一性的磷脂酶C/二酰甘油脂肪酶/单酰甘油脂肪酶途径释放出来的。溶解的DG脂肪酶和MG脂肪酶能在巴塞尔胞液游离Ca~(2+)&gt；浓度范围内对底物进行降解。随后，利用钙离子载体A23187分析了胞内游离钙浓度与AA代谢物形成的关系。胶原蛋白在胞浆基础状态下能诱导少量AA的释放。然而，由于胶原受体占位和Ca~(2+)水平升高，磷脂酶A_2可诱导大量AA的释放。作为TXA2模拟激动剂，STA2可引起除AA释放外的所有反应。根据这些结果，对胶原激活的人血小板释放AA和信号转导的机制进行了讨论。

We have indicated that several nanomolar thromboxane A_2 (TXA_2) originating from inositollipids may directly cause Ca^<2+> mobilization in human platelets during activation with collagen.The mechanism of arachidonic acid (AA) release in collagen-activated human platelets was studied. An arachidonic acid metabolite, thromboxane B_2, was formed in parallel with the formation of phosphatidic acid without fomation of lysophosphatidic acid or lysophosphatidylinositol in the absence of extracellular Ca^<2+>, suggesting that AA was released from PI via a PI-specific phospholipase C/diacylglycerol lipase/monoacylglycerol lipase pathway under the cytosolic low Ca^<2+> concentrations. Moreover, solubilized DG lipase and MG lipase could hydrolyze the substrates at basel cytosolic free Ca^<2+> concentrations. Subsequently, the relationship of cytosolic free Ca^2 concentrations and formation of AA metabolites was analyzed using Ca^<2+> ionophore, A23187. Collagen was able to induce a release of small amounts of AA under basal cytosolic Ca^<2+> conditions. However, a release of large amounts of AA was induced by phospholipase A_2 activated by both collagen-receptor occupancy and elevated Ca^<2+> levels. A TXA_2 mimetic agonist, STA_2 induced all the responses except for AA release. From these results, the mechanism of AA release and signal transduction in collagen-activated human platelets is discussed.