Maruyama I, Majerus P W
Blood. 1987 May;69(5):1481-4.
We investigated the effect of protein C on the endocytosis of thrombin-thrombomodulin complexes. We previously showed that exposure of umbilical vein endothelial cells to thrombin stimulated the internalization and degradation of thrombin. A similar internalization was stimulated by a monoclonal antithrombomodulin antibody. We have repeated these studies in the presence of protein C and found that endocytosis of 125I-thrombin-thrombomodulin complexes, but not 125I-antithrombomodulin-thrombomodulin complexes, is inhibited. Activated protein C did not inhibit endocytosis of thrombin-thrombomodulin complexes. Protein C inhibited both internalization and degradation of 125I-thrombin and diisopropylphosphoryl (DIP) 125I-thrombin in human lung cancer cells (A549). These effects were observed at protein C concentrations found in human plasma. Protein S had no effect on the inhibition of endocytosis of thrombin-thrombomodulin complexes by protein C. We propose that protein C may regulate the rate of endocytosis of thrombin-thrombomodulin complexes in vivo and thereby control the capacity for endothelium to activate protein C.
我们研究了蛋白C对凝血酶-血栓调节蛋白复合物内吞作用的影响。我们之前表明，将脐静脉内皮细胞暴露于凝血酶会刺激凝血酶的内化和降解。一种抗血栓调节蛋白单克隆抗体也能刺激类似的内化过程。我们在有蛋白C存在的情况下重复了这些研究，发现125I-凝血酶-血栓调节蛋白复合物的内吞作用受到抑制，但125I-抗血栓调节蛋白-血栓调节蛋白复合物的内吞作用未受抑制。活化蛋白C并未抑制凝血酶-血栓调节蛋白复合物的内吞作用。蛋白C抑制了人肺癌细胞（A549）中125I-凝血酶和二异丙基磷酰（DIP）125I-凝血酶的内化及降解。在人血浆中发现的蛋白C浓度下可观察到这些效应。蛋白S对蛋白C抑制凝血酶-血栓调节蛋白复合物内吞作用没有影响。我们提出，蛋白C可能在体内调节凝血酶-血栓调节蛋白复合物的内吞速率，从而控制内皮细胞激活蛋白C的能力。
