DEFIBROTIDE STIMULATES EXPRESSION OF THROMBOMODULIN IN HUMAN ENDOTHELIAL-CELLS

Cultured human umbilical vein endothelial cells were incubated with de fibrotide at concentrations of 0, 5, 50 and 500 mu g/ml for 4 and 24 h respectively. Thrombomodulin activity and molecules on the surface of the cells were determined by chromogenic assay and radioimmunoassay, thrombomodulin antigen in endothelial cells and in conditioned medium of the cells was measured by immunoradioassay. Thrombomodulin mRNA wit hin the cells was analysed by slot blot. After 24 h of incubation, the activity and molecules of thrombomodulin on the surface of endothelia l cells, as well as the antigen and mRNA of thrombomodulin in the cell s were significantly increased in a dose dependent manner. However, th e level of thrombomodulin antigen in conditioned medium was about equa l to that of the control. Our data indicate that defibrotide stimulate s expression of thrombomodulin in human endothelial cells. These benef icial effects may play a role in antithrombotic activity of defibrotid e.