Surface and fluid phase activities of two forms of activated Hageman factor produced during contact activation of plasma.
Surface and fluid phase activities of two forms of activated Hageman factor produced during contact activation of plasma.
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DOI：
10.1084/jem.147.3.719
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发表时间：
1978-03-01
期刊：
影响因子：
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通讯作者：
Griffin JH
中科院分区：
文献类型：
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作者：
Revak SD;Cochrane CG;Bouma BN;Griffin JH
本文研究了血浆接触激活时产生的两种形式的活化Hageman因子(HFA)激活前激肽释放酶和凝血因子XI的能力。α-HFA是一种与表面结合的80000分子质量的双链酶，能够裂解表面结合的前激肽释放酶和凝血因子XI。β-HFA是一种28,000摩尔重量的单链分子，在接触激活时从表面释放出来，能够切割前激肽释放酶，但对因子XI没有活性。无论底物是表面结合的还是在溶液中，前激肽释放酶都会被β-HFA切割。因子XI只有在表面结合时才发生切割，并且只有α-形式的HFA才能进行这种蛋白分解作用。发现XI因子仍与表面结合，而前激肽释放酶和激肽释放酶迅速从表面解离到上清液。这些发现表明，通过激活因子XI启动的内源性凝血是发生在接触激活部位的局部事件，是α-HFA作用的结果。相反，激肽释放酶形成的激肽生成和纤溶作用可以通过α-HFA作用在接触激活部位启动，也可以通过β-HFA在整个血浆中启动；这些活动的进一步传播是由激肽释放酶本身从表面快速解离所确保的。
The ability of the two forms of activated Hageman factor (HFa) produced during contact activation of plasma to activate prekallikrein and factor XI was studied. alpha-HFa, defined as an 80,000 mol wt two-chain enzyme which remains bound to the surface was capable of cleaving surface-bound prekallikrein and factor XI. beta-HFa, a 28,000 mol wt single chain molecule, released from the surface during contact activation was able to cleave prekallikrein but showed no activity on factor XI. Cleavage of prekallikrein by beta-HFa occurred irrespective of whether the substrate was surface-bound or in solution. Cleavage of factor XI occurred only when it was surface bound and only the alpha- form of HFa was capable of this proteolytic action. Factor XI was found to remain bound to the surface while prekallikrein and kallikrein rapidly dissociated from the surface into the supernate. These findings suggest that the initiation of intrinsic coagulation through the activation factor XI is a localized event occurring at the site of contact activation and is the result of the action of alpha-HFa. By contrast, kinin generation and fibrinolysis resulting from the formation of kallikrein can be initiated either at the site of contact activation, by alpha-HFa action, or throughout the plasma, by beta-HFa; further dissemination of these activities is assured by the rapid dissociation of kallikrein itself from the surface.