España F, Ratnoff O D
J Lab Clin Med. 1983 Oct;102(4):487-99.
Hageman factor (HF, factor XII), adsorbed to negatively charged agents, is transformed to an activated state in which it initiates reactions of the intrinsic pathway of thrombin formation by activating plasma thromboplastin antecedent (PTA, factor XI). High-molecular-weight kininogen (HMWK, Fitzgerald factor) and plasma prekallikrein accelerate these early steps in the clotting process. Questions have been raised about the role of HMWK in the activation of Hageman factor by surfaces. In the present studies, we report that the activation of purified human HF by sulfatides, ellagic acid, kaolin, or glass occurred in the absence of HMWK. Indeed, small amounts of HMWK inhibited activation of HF by ellagic acid. Physiological concentration of HMWK had little or no influence on the activation of HF by sulfatides, kaolin, or glass, but higher concentrations (3 to 6 times more) showed the same inhibitory effect as after activation by ellagic acid. This inhibitory property of HMWK may be attributed to competitive binding of HF and HMWK on the surface of the activating agents. In fact, when HF was added to kaolin or glass that had been incubated with HMWK and then washed, the inhibitory effect persisted, indicating HMWK that was bound to the surface blocked activation of HF. Studies with 125I-HF and 125I-HMWK supported this interpretation. Plasma prekallikrein accelerated activation of the amidolytic properties of HF by sulfatides, kaolin, or glass but did not influence activation of HF by ellagic acid. In the presence of plasma kallikrein, HMWK at moderate concentrations slightly accelerated the rate of activation of HF by activating agents other than ellagic acid. Higher concentrations of HMWK counteracted both the accelerating effect of prekallikrein and the inhibitory effect observed when HF was incubated with an excess of kaolin. These experiments, then, support the view that the procoagulant function of HMWK is localized to a point subsequent to the activation of HF.
吸附于带负电荷物质的哈格曼因子（HF，因子Ⅻ）会转变为活化状态，在此状态下，它通过激活血浆促凝血酶原激酶（PTA，因子Ⅺ）启动凝血酶形成的内源性途径反应。高分子量激肽原（HMWK，菲茨杰拉德因子）和血浆前激肽释放酶会加速凝血过程中的这些早期步骤。关于HMWK在表面激活哈格曼因子过程中的作用，人们提出了一些问题。在本研究中，我们报告，在不存在HMWK的情况下，硫酸脑苷脂、鞣花酸、高岭土或玻璃可激活纯化的人HF。事实上，少量的HMWK会抑制鞣花酸对HF的激活。生理浓度的HMWK对硫酸脑苷脂、高岭土或玻璃激活HF几乎没有影响，但较高浓度（高3至6倍）的HMWK显示出与鞣花酸激活后相同的抑制作用。HMWK的这种抑制特性可能归因于HF和HMWK在激活剂表面的竞争性结合。实际上，当将HF添加到已与HMWK孵育然后洗涤过的高岭土或玻璃中时，抑制作用仍然存在，这表明结合在表面的HMWK会阻止HF的激活。用¹²⁵I-HF和¹²⁵I-HMWK进行的研究支持了这一解释。血浆前激肽释放酶可加速硫酸脑苷脂、高岭土或玻璃对HF酰胺水解特性的激活，但不影响鞣花酸对HF的激活。在血浆激肽释放酶存在的情况下，中等浓度的HMWK会通过激活除鞣花酸以外的其他激活剂，略微加速HF的激活速率。较高浓度的HMWK会抵消前激肽释放酶的加速作用以及当HF与过量高岭土孵育时观察到的抑制作用。因此，这些实验支持这样一种观点，即HMWK的促凝血功能定位于HF激活之后的某个点。
