Seligsohn U, Osterud B, Brown S F, Griffin J H, Rapaport S I
J Clin Invest. 1979 Oct;64(4):1056-65. doi: 10.1172/JCI109543.
Factor VII can be activated, to a molecule giving shorter clotting times with tissue factor, by incubating plasma with kaolin or by clotting plasma. The mechanisms of activation differ. With kaolin, activated Factor XII (XII(a)) was the apparent principal activator. Thus, Factor VII was not activated in Factor XII-deficient plasma, was partially activated in prekallikrein and high-molecular weight kininogen (HMW kininogen)-deficient plasmas, but was activated in other deficient plasmas. After clotting, activated Factor IX (IX(a)) was the apparent principal activator. Thus, Factor VII was not activated in Factor XII-,HMW kininogen-, XI-, and IX-deficient plasmas, but was activated in Factor VIII-, X-, and V-deficient plasmas. In further studies, purified small-fragment Factor XII(a) (beta-XII(a)), kallikrein, and Factor IX(a) were added to partially purified Factor VII and to plasma. High concentrations of beta-XII(a) activated Factor VII in a purified system; much lower concentrations of beta-XII(a) activated Factor VII in normal plasma but not in prekallikrein or HWM kininogen-deficient plasmas. Kallikrein alone failed to activate partially purified Factor VII but did so when purified Factor IX was added. Kallikrein also activated Factor VII in normal, Factor XII-, and Factor IX-deficient plasmas. Purified Factor IX(a) activated partially purified Factor VII and had no additional indirect activating effect in the presence of plasma. These results demonstrate that both Factor XII(a) and Factor IX(a) directly activate human Factor VII, whereas kallikrein, through generation of Factor XII(a) and Factor IX(a), functions as an indirect activator of Factor VII.
通过将血浆与高岭土孵育或使血浆凝固，因子VII可被激活为一种与组织因子结合时凝血时间更短的分子。激活机制有所不同。使用高岭土时，活化的因子XII（XII(a)）是明显的主要激活剂。因此，因子VII在缺乏因子XII的血浆中未被激活，在缺乏前激肽释放酶和高分子量激肽原（HMW激肽原）的血浆中部分被激活，但在其他缺乏相关因子的血浆中被激活。凝血后，活化的因子IX（IX(a)）是明显的主要激活剂。因此，因子VII在缺乏因子XII、HMW激肽原、因子XI和因子IX的血浆中未被激活，但在缺乏因子VIII、因子X和因子V的血浆中被激活。在进一步的研究中，将纯化的小片段因子XII(a)（β-XII(a)）、激肽释放酶和因子IX(a)添加到部分纯化的因子VII和血浆中。高浓度的β-XII(a)在纯化系统中激活因子VII；低得多的β-XII(a)浓度在正常血浆中激活因子VII，但在缺乏前激肽释放酶或HWM激肽原的血浆中则不能。单独的激肽释放酶未能激活部分纯化的因子VII，但添加纯化的因子IX时则可激活。激肽释放酶也在正常、缺乏因子XII和缺乏因子IX的血浆中激活因子VII。纯化的因子IX(a)激活部分纯化的因子VII，并且在有血浆存在时没有额外的间接激活作用。这些结果表明，因子XII(a)和因子IX(a)都能直接激活人因子VII，而激肽释放酶通过生成因子XII(a)和因子IX(a)，作为因子VII的间接激活剂发挥作用。
