Walsh P N, Sinha D, Kueppers F, Seaman F S, Blankstein K B
Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
J Clin Invest. 1987 Dec;80(6):1578-86. doi: 10.1172/JCI113244.
We have studied the complex interrelationships between platelets, Factor XIa, alpha 1-protease inhibitor and Factor IX activation. Platelets were shown to secrete an inhibitor of Factor XIa, and to protect Factor XIa from inactivation in the presence of alpha 1-protease inhibitor and the secreted platelet inhibitor. This protection of Factor XIa did not arise from the binding of Factor XIa to platelets, the presence of high molecular weight kininogen, or the inactivation of alpha 1-protease inhibitor by platelets. The formation of a complex between alpha 1-protease inhibitor and the active-site-containing light chain of Factor XIa was inhibited by activated platelets and by platelet releasates, but not by high molecular weight kininogen. These results support the hypothesis that platelets can regulate Factor XIa-catalyzed Factor IX activation by secreting an inhibitor of Factor XIa that may act primarily outside the platelet microenvironment and by protecting Factor XIa from inhibition, thereby localizing Factor IX activation to the platelet plug.
我们研究了血小板、因子XIa、α1-蛋白酶抑制剂和因子IX激活之间复杂的相互关系。研究表明，血小板可分泌因子XIa抑制剂，并在α1-蛋白酶抑制剂和分泌的血小板抑制剂存在的情况下保护因子XIa不被灭活。因子XIa的这种保护作用并非源于因子XIa与血小板的结合、高分子量激肽原的存在，也不是由于血小板使α1-蛋白酶抑制剂失活。活化的血小板和血小板释放物可抑制α1-蛋白酶抑制剂与因子XIa含活性位点的轻链形成复合物，但高分子量激肽原则无此作用。这些结果支持这样一种假说，即血小板可通过分泌一种可能主要在血小板微环境外起作用的因子XIa抑制剂，并保护因子XIa不被抑制，从而将因子IX的激活定位在血小板凝块处，进而调节因子XIa催化的因子IX激活。
