Protein C inhibits endocytosis of thrombin-thrombomodulin complexes in A549 lung cancer cells and human umbilical vein endothelial cells.
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.
D002460:Cell Line; D004705:Endocytosis / Q000187:drug effects*; D004727:Endothelium / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D004789:Enzyme Activation; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D011485:Protein Binding; D011486:Protein C / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism*; D018179:Receptors, Thrombin; D013917:Thrombin / Q000378:metabolism*; D013997:Time Factors; D014471:Umbilical Veins
D007457:Iodine Radioisotopes; D011486:Protein C; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D013917:Thrombin