The Effect of Cycolsporine A on the Expression of Von Willebrand Factor in Human Glomerular Endothelial Cells / 대한신장학회잡지

ABSTRACT

Cyclosporine(CsA) is a modulator of the immune system used therapeutically to prevent organ transplant rejection. However, it is nephrotoxic and causes thrombotic phenomena after renal and bone marrow transplantation. CsA nephrotoxicity in vivo is associated with elevated levels of von Willebrand factor(vWf), which is a multimeric plasm glycoprotein secreted by endothelial cells and platelets. CsA is not soluble in water and the intravenous form given to patients is dissolved in a vehicle called cremophor EL. The vehicle has been implicated in anaphylatic reactions and associated with the release of histamine in vivo. We hypothesized that CsA or cremophor might affect the release of vWf from human glomerular endothelial cells. vWf was measured in culture supernant using ELISA kit after speed vaccum for 3 hour. The expression of vWf in cultured human glomerular endothelial cells was relatively low compared to human plasm in vivo. CsA alone did not increase vWf release(100%, 99.9+/-0.7%, 99.1+/-2.9%, 106+/-21.5%, CsA 0, 0.1, 1, 10microM mean S.E., n=2), but cremophor EL increased vWf release (100%, 104.0+/-8.6%, 117.6+/-9.5%, 121.3+/-12.2%, mean+/-S.E., n=3). These results were same as the results of experiments under thrombin(1IU/ml) and histamine(10(-4)M). The increased expression of vWf in human glomerular endothelial cells in response to CsA seems to be related to cremophor, the solvent, rather than CsA itself in vitro culture experiments.