Inhibition of cell-mediated cytolysis and P-glycoprotein function in natural killer cells by verapamil isomers and cyclosporine a analogs

摘要: We have previously shown that among normal leukocytes, CD56+ and CD8+ cells express relatively high levels of P-glycoprotein (P-gp), a transmembrane efflux pump. While the physiologic significance P-gp expression in leukocytes is unknown, suggest may function cell-mediated cytolysis. To explore this possibility we examined effect four inhibitors [(R)-verapamil (R-ver), (S) -verapamil (S-ver), cyclosporine A (CsA), PSC833 (PSC)] on both inhibition natural killer cell (NK) efflux. NK was assayed by measuring lysis of51Cr-labeled K562 target presence absence inhibitors. All inhibited NK-mediated cytolysis dose-dependent manner. The stereoisomers verapamil were more potent than cyclosporines CsA PSC. In contrast, PSC as P-gp-mediated rhodamine 123 dye isomers. Both maximally at 3μM, but only minimally compounds demonstrated closer correlation between data support role for cytolysis; however, these studies also cytolytic process multifaceted mechanism partially abrogates process.