Summary
Cultured human umbilical vein endothelial cells were incubated with defibrotide at
concentrations of 0, 5, 50 and 500 jxg/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 within the
cells was analysed by slot blot. After 24 h of incubation, the activity and molecules
of thrombomodulin on the surface of endothelial cells, as well as the antigen and
mRNA of thrombomodulin in the cells were significantly increased in a dose dependent
manner. However, the level of thrombomodulin antigen in conditioned medium was about
equal to that of the control. Our data indicate that defibrotide stimulates expression
of thrombomodulin in human endothelial cells. These beneficial effects may play a
role in antithrombotic activity of defibrotide.
