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Cyclosporine A가 사구체내 내피세포의 von Willebrand factor 발현에 미치는 영향 |
박수길 , 김승후 , 양원석 , 김청수 , 안한종 , 박정식 , 이재담 |
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Abstract |
Cyclosporine(CsA) is a modulator of the immune system used therapeutically to prevent organ trans- plant rejection. However, it is nephrotoxic and cau- ses thrombotic phenomena after renal and bone ma- rrow transplantation. CsA nephrotoxicity in vivo is associated with elevated levels of von Willebrand factor(vWf), which is a multimeric plasm glycopro- tein secreted' by endothelial cells and platelets. CsA is not soluble in water and the intravenous form gi- ven to patients is dissolved in a vehicle called cre- rnophor EL. The vehicle has been implicated in anaphylatic reactions and associated with the release of histarnine in vivo. We hypothesized that CsA or cremophor might affect the release of vWf from human glomerular endothelial cells. vWf was measu- red in culture supemant using ELISA kit after speed vaccum for 3 hour. The expression of vWf in cultu- red 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±2.99%, 106±21.5%, CsA 0, 0.1, 1, 10mM 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 hista-mine(10 'M). The increased expression of vWf in human glomerular endothelial cells in response to CsA seems to be related to crernophor, the solvent, rather than CsA itself in vitro culture experiments. |
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