THROMBIN-MEDIATED RELEASE OF FACTOR-VIII ANTIGEN FROM HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS IN CULTURE

Abstract

The effects of purified human .alpha.-thrombin on factor VIII antigen (FVIII-Ag) release by human umbilical vein endothelial cells in culture were examined. .alpha.-Thrombin induced a time- and dose-dependent release of FVIII-Ag into supernatant medium. Thrombin-mediated FVIII-Ag release was not dependent on protein synthesis and was observed in both serum-free and serum-containing media. FVIII-Ag release was prevented when the serine esterase activity of thrombin was inhibited. Pretreatment of human endothelial cells with .alpha.-thrombin, but not diisofluorophosphate-thrombin, prevented subsequent FVIII-Ag release by .alpha.-thrombin. Thrombin-mediated FVIII-Ag release was not associated with significant 51Cr release from prelabeled endothelial monolayers. .alpha.-Thrombin induces release of preformed FVIII-Ag from human umbilical vein endothelial cells by a receptor-independent, nonlytic mechanism requiring serine esterase activity.