Fibrinogen blocks the autoactivation and thrombin-mediated activation of factor XI on dextran sulfate.
Fibrinogen blocks the autoactivation and thrombin-mediated activation of factor XI on dextran sulfate.
复制标题
纤维蛋白原阻断硫酸葡聚糖上 XI 因子的自激活和凝血酶介导的激活。
DOI：
10.1073/pnas.89.23.11189
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发表时间：
1992
影响因子：
11.1
通讯作者：
Colman,RW
中科院分区：
文献类型：
--
作者：
Scott,CF;Colman,RW
当三种接触系统酶之一的XIa因子产生并激活IX因子时，血液凝固的内在途径被激活。研究表明，在体外，当因子XI通过其辅助因子高分子量激肽原（HK）转运到表面后，因子XI可以被表面结合因子XIIa有效地激活。然而，缺乏三种接触系统蛋白中的任何一种的个体，即因子XII、prekallikrein和HK，不会出现出血异常。这个谜团促使一些研究人员寻找XI因子的“替代”激活途径。最近，有报道称因子XI在可溶性的“表面”硫酸葡聚糖上被自激活，凝血酶被证明可以加速这种自激活。然而，也有报道称，因子xiia介导的因子XI激活的辅因子HK实际上降低了凝血酶催化的因子XI的激活率。尽管如此，有人认为凝血酶是一种比XIIa因子更有效的激活剂。在本报告中，我们研究了血浆中主要凝血蛋白纤维蛋白原对因子XI激活率的影响。纤维蛋白原是血浆中凝血酶的首选底物，它实际上阻止了因子XI的自身活化以及凝血酶介导的因子XI的活化，而对因子xiia催化的活化没有影响。除了凝血酶介导的激活外，HK显著地抑制了因子XI的自激活。这些数据表明，因子XI在血浆环境中不会自动激活，因此凝血酶不太可能增强激活。我们认为，因子XI激活的“缺失途径”仍然是一个谜，值得进一步研究。
The intrinsic pathway of blood coagulation is activated when factor XIa, one of the three contact-system enzymes, is generated and then activates factor IX. Factor XI has been shown to be efficiently activated in vitro by surface-bound factor XIIa after factor XI is transported to the surface by its cofactor, high molecular weight kininogen (HK). However, individuals lacking any of the three contact-system proteins--namely, factor XII, prekallikrein, and HK--do not suffer from bleeding abnormalities. This mystery has led several investigators to search for an "alternate" activation pathway for factor XI. Recently, factor XI has been reported to be autoactivated on the soluble "surface" dextran sulfate, and thrombin was shown to accelerate the autoactivation. However, it was also reported that HK, the cofactor for factor XIIa-mediated activation of factor XI, actually diminishes the thrombin-catalyzed activation rate of factor XI. Nonetheless, it was suggested that thrombin was a more efficient activator than factor XIIa. In this report we investigated the effect of fibrinogen, the major coagulation protein in plasma, on the activation rate of factor XI. Fibrinogen, the preferred substrate for thrombin in plasma, virtually prevented autoactivation of factor XI as well as the thrombin-mediated activation of factor XI, while having no effect on factor XIIa-catalyzed activation. HK dramatically curtailed the autoactivation of factor XI in addition to the thrombin-mediated activation. These data indicate that factor XI would not be autoactivated in a plasma environment, and thrombin would, therefore, be unlikely to potentiate the activation. We believe that the "missing pathway" for factor XI activation remains an enigma that warrants further investigation.