细胞骨架对凝血酶诱导人血小板分泌反应的调节(英文)

本文利用血小板表面外露的GMP-140为血小板分泌反应的特异性标志,通过放射免疫分析法定量测定血小板表面GMP-140分子数,研究了细胞骨架抑制剂对凝血酶诱导血小板分泌反应的影响。结果表明,凝血酶激活使血小板表面GMP-140的外露明显增加,反应迅速,并在一定范围内呈剂量和时间依赖性;而ADP刺激则几乎不引起GMP-140外露的增加。凝血酶激活前加入不同的细胞骨架抑制剂处理可产生不同的效应:细胞松驰素B(肌动蛋白微丝抑制剂)可明显上调凝血酶诱导的GMP-140外露;而秋水仙素(微管抑制剂)则下调GMP-140的外露;两者同时处理仍呈现明显的上调作用。提示凝血酶作为一种强激活剂,不仅可通过受体-G蛋白-第二信使的途径启动血小板分泌反应,而且可能经诱导肌动蛋白微丝的形成对分泌反应起反馈性负调节作用。微管的存在则可能对凝血酶诱导的分泌反应起促进作用。虽然两种细胞骨架的作用相反,但以微丝的作用为主,两者间无相互拮抗现象。

EVIDENCE FOR THROMBIN-INDUCED HUMAN PLATELET SECRETION REGULATED BY THE CYTOSKELETON

The effects of cytoskeleton on throm-bin-induced platelet secretion were studied with detecting the molecular number of GMP-140 exposed on platelet surface by radioimmunoassay. It was seen that thro-mbin could stimulate a rapid exposure of a large amount of GMP-140. while ADP only caused a little increase of exposed GMP-140. The response induced by thro-mbin was dose-dependent and related to incubation time. Treatment with different cytoskeleton inhibitors prior to thrombin resulted in distinct responses. Cytochalasin B, an actin-microfilament inhibitor, could remarkably upregulate thrombin-induced GMP-140 exposure. Contrarily, colchicine, a microtubular inhibitor, leaded to a do-wnregulation of GMP-140 molecular number. A significant upregulation of GMP-140 exposure also occured on the platelets treated simultaneously with both cytocha-lasin B and colchicine. These results suggested that thrombin induced formation of actin filaments may counterregulate platelet secretion, whereas microtubules may promote it. There seemed to be no antagonistic interaction between these two classes of cytoskeleton.