Cochrane C G, Griffin J H
Am J Med. 1979 Oct;67(4):657-64. doi: 10.1016/0002-9343(79)90253-5.
Data obtained in the past few years have defined the molecular mechanisms of contact activation of the Hageman factor pathways of plasma, i.e., the kinin-forming, intrinsic clotting and fibrinolytic systems. Involved are four molecules: Hageman factor, high molecular weight (MW) kininogen, prekallikrein and factor XI. High MW kininogen serves as a surface cofactor to assemble prekallikrein or factor XI in proximity to surface-bound Hageman factor. Reciprocal proteolytic activation of Hageman factor and prekallikrein represents an essential step in the rapid activation of the contact phase. Although Hageman factor does undergo cleavage and activation in the absence of prekallikrein or high MW kininogen, the rate is approximately 50 and 100 times slower than when these molecules are present. Once Hageman factor is activated on the surface, it cleaves and activates clotting factor XI. Activated Hageman factor (HFa) exhibits two molecular forms. One of these, alpha HFa, activates prekallikrein and factor XI, and the intrinsic clotting system on the surface. alpha HFa and clotting factor XI remain surface bound. The other form of activated Hageman factor, beta HFa, leaves the surface, going into solution where it readily activates additional prekallikrein but not factor XI. Of perhaps even greater importance, kallikrein rapidly dissociates from the surface. Thus the formation of bradykinin and fibrinolysis is disseminated whereas clotting via the intrinsic system remains localized. Reviewed here is the molecular mechanism of contact activation of the Hageman factor pathways and discussed in the interaction of Hageman factor with the negatively charged surface, prekallikrein, factor XI and high MW kininogen. The multiple forms of activated Hageman factor and their potential biologic significance are also discussed.
过去几年获得的数据已明确了血浆中Hageman因子途径（即激肽形成系统、内源性凝血系统和纤维蛋白溶解系统）接触激活的分子机制。涉及的四种分子为：Hageman因子、高分子量（MW）激肽原、前激肽释放酶和因子XI。高分子量激肽原作为一种表面辅因子，在与表面结合的Hageman因子附近组装前激肽释放酶或因子XI。Hageman因子和前激肽释放酶的相互蛋白水解激活是接触相快速激活的关键步骤。虽然在没有前激肽释放酶或高分子量激肽原的情况下，Hageman因子确实会发生裂解和激活，但其速率比这些分子存在时慢约50倍和100倍。一旦Hageman因子在表面被激活，它就会裂解并激活凝血因子XI。激活的Hageman因子（HFa）呈现两种分子形式。其中一种，α-HFa，激活前激肽释放酶和因子XI以及表面的内源性凝血系统。α-HFa和凝血因子XI仍与表面结合。激活的Hageman因子的另一种形式，β-HFa，离开表面进入溶液，在其中它很容易激活额外的前激肽释放酶，但不能激活因子XI。也许更重要的是，激肽释放酶迅速从表面解离。因此，缓激肽的形成和纤维蛋白溶解得以扩散，而内源性系统的凝血仍局限于局部。本文综述了Hageman因子途径接触激活的分子机制，并讨论了Hageman因子与带负电荷表面、前激肽释放酶、因子XI和高分子量激肽原的相互作用。还讨论了激活的Hageman因子的多种形式及其潜在的生物学意义。
