The mechanism of the initiation ractions for the intrinsic blood coagulation,kinin release and fibrinolysis: the activation mechanism of the precursor of serine proteases by negatively-charged surfaces and gheir biological significance.

内在凝血的起始反应是由丝氨酸蛋白酶的前体因子XII与带负电荷的表面相互作用触发的，这导致前体转化为活性蛋白酶。该反应也是纤溶系统和激肽释放系统的起始反应。虽然这些反应被认为在止血中起重要作用，但其生物学意义仍有待确定。本研究旨在阐明(1)丝氨酸蛋白酶前体与带负电荷表面相互作用后如何引起有限的蛋白水解；(2)因子XII激活反应的生物学意义。研究结果如下：(1)结合纯化的凝血因子，重构了内在凝血的起始反应，建立了测定凝血因子XII活化的灵敏方法。发现与高岭土、硫脂和硫酸多糖的活化反应不仅依赖于表面浓度和凝血因子，而且还依赖于金属离子（特别是锌离子）和氯化钠的浓度。血小板对表面与血小板释放的阳离子蛋白相互作用的反应表现出较强的抑制活性。(2)建立了激肽原的放射免疫测定方法，分析了正常大鼠和HMW激肽原缺乏大鼠在炎症诱导下产生的激肽原（t -激肽原）。我们还分析了大鼠、豚鼠、牛、兔和猕猴血浆的内在凝血和prekallikin的激活情况，并与人血浆进行了比较。我们可以发现，一些动物如豚鼠和大鼠对因子XII的激活非常敏感，而一些动物如牛、兔和美洲虎对因子XII的激活非常抵抗。

The initiation reaction of the intrinsic blood coagulation is triggered by the interaction of a precursor of serine protease, Factor XII, with negativelycharged surfaces, which leads to the transformation of the precursor to active protease. This reaction is also the initiation reactions of the fibrinolytic system and kinin-releasing system. Although these reactions are considered to play important roles in the hemostasis, their biological significance remains to be established. This study was undertaken to clarify, (1) how the limited proteolysis of the precursors of serine proteases is caused after the interaction with negatively-charged surfaces and (2) what the biological significance of the activation reaction of Factor XII is.The results are as follows;(1) The initiation reactions of the intrinsic blood coagulation were reconstituted by the combination of ghe purified coagulation factors and the sensitive method to measure the activation of Factor XII was established. The activation reactions with kaolin, sulfatide and polysaccharide sulfate were found to be dependent not only on the concentrations of the surfaces and the coagulation factors, but also on the concentration of metal ions, particularly, zinc ion, and of sodium chloride. Platelets showed the strong inhibitory activity to the reactions by the interaction of the surfaces with the cationic proteins liberated from platelets.(2) We established the radioimmunoassay method for kininogens and andalyzed the kininogens (T-kininogens) which increased by the induction of inflammation using normal and HMW kininogen-deficient rats. We also analyzed the intrinsic blood coagulation and the activation of prekallikrein in the plasmas of rat, guineapig, ox, rabbit and sunkus, comparing with those of human plasma. We could find that some animals such as guinea-pig and rat are very sensitive in the activation of Factor XII and that some animals such as ox, rabbit and sunkus are very resistant in the actilvation.