Brower M S, Walz D A, Garry K E, Fenton J W
Blood. 1987 Mar;69(3):813-9.
During blood coagulation, polymorphonuclear leukocytes release elastase in amounts that can exceed 100 nmol/L. We therefore studied the interaction between human leukocyte elastase and human alpha-thrombin. Elastase cleaved the thrombin B chain (Ala 150-Asn 151) near the gamma-cleavage site, resulting in two fragments held together by noncovalent interactions. The NH2-terminal fragment (FI), mol wt approximately 18,000, was disulfide-linked to the thrombin A chain. The COOH-terminal fragment (FII), mol wt approximately 13,000, contained the active-site serine and formed a covalent bond with antithrombin III. Heparin accelerated proteolysis of alpha-thrombin by elastase. Proteolyzed alpha-thrombin (T theta) retained full amidolytic activity; however, the concentration of T theta causing 50% maximal platelet aggregation and adenosine triphosphate (ATP) release was 7.9 nmol/L (1.1 nmol/L for alpha-thrombin and 220 nmol/L for gamma-thrombin). Fibrinogen clotting activity of T theta and gamma-thrombin was 32% and 1% that of alpha-thrombin, respectively. Elastase released during the coagulation process may modulate thrombin activity. In addition, elastase-modified thrombin may be a useful probe of the structure and function of the gamma-cleavage region.
在血液凝固过程中，多形核白细胞释放的弹性蛋白酶量可超过100 nmol/L。因此，我们研究了人白细胞弹性蛋白酶与人α-凝血酶之间的相互作用。弹性蛋白酶在γ-裂解位点附近切割凝血酶B链（Ala 150-Asn 151），产生两个通过非共价相互作用结合在一起的片段。NH2末端片段（FI），分子量约为18,000，通过二硫键与凝血酶A链相连。COOH末端片段（FII），分子量约为13,000，含有活性位点丝氨酸，并与抗凝血酶III形成共价键。肝素加速了弹性蛋白酶对α-凝血酶的蛋白水解作用。经蛋白水解的α-凝血酶（Tθ）保留了完整的酰胺水解活性；然而，引起50%最大血小板聚集和三磷酸腺苷（ATP）释放的Tθ浓度为7.9 nmol/L（α-凝血酶为1.1 nmol/L，γ-凝血酶为220 nmol/L）。Tθ和γ-凝血酶的纤维蛋白原凝血活性分别为α-凝血酶的32%和1%。凝血过程中释放的弹性蛋白酶可能调节凝血酶活性。此外，弹性蛋白酶修饰的凝血酶可能是γ-裂解区域结构和功能的有用探针。
