Pratt C W, Church F C, Pizzo S V
Department of Biochemistry, Duke University Medical Center, Durham, North Carolina.
Arch Biochem Biophys. 1988 Apr;262(1):111-7. doi: 10.1016/0003-9861(88)90173-7.
The plasma clearance of 125I-labeled human heparin cofactor II and its complex with thrombin was studied in mice to determine whether a specific mechanism exists for the catabolism of the inhibitor-proteinase complex. Initial studies demonstrated that murine plasma contains a heparin cofactor II-like inhibitor as shown by the presence of a dermatan sulfate-sensitive thrombin inhibitor. Human heparin cofactor II cleared from the circulation of mice with an apparent half-life of 80 min while heparin cofactor II-thrombin complexes cleared with an apparent half-life of only 10 min. The specificity of the clearance mechanism was investigated by clearance competition studies involving coinjection of excess unlabeled heparin cofactor II-alpha-thrombin, antithrombin III-alpha-thrombin, or alpha 1-proteinase inhibitor-elastase, and by tissue distribution studies. The results demonstrated that the clearance of 125I-labeled heparin cofactor II-alpha-thrombin is a receptor-mediated process, and that the same hepatocyte receptor system recognizes complexes containing heparin cofactor II, antithrombin III, and alpha 1-proteinase inhibitor.
在小鼠中研究了125I标记的人肝素辅因子II及其与凝血酶复合物的血浆清除率，以确定抑制剂-蛋白酶复合物的分解代谢是否存在特定机制。初步研究表明，鼠血浆中含有一种类肝素辅因子II抑制剂，硫酸皮肤素敏感的凝血酶抑制剂的存在证明了这一点。人肝素辅因子II从小鼠循环中清除的表观半衰期为80分钟，而肝素辅因子II-凝血酶复合物清除的表观半衰期仅为10分钟。通过涉及共同注射过量未标记的肝素辅因子II-α-凝血酶、抗凝血酶III-α-凝血酶或α1-蛋白酶抑制剂-弹性蛋白酶的清除竞争研究以及组织分布研究，对清除机制的特异性进行了研究。结果表明，125I标记的肝素辅因子II-α-凝血酶的清除是一个受体介导的过程，并且相同的肝细胞受体系统识别含有肝素辅因子II、抗凝血酶III和α1-蛋白酶抑制剂的复合物。
