LIPID TRANSFER PROTEIN-I FACILITATED TRANSFER OF CYCLOSPORINE FROM LOW-TO HIGH-DENSITY-LIPOPROTEINS IS ONLY PARTIALLY DEPENDENT ON ITS CHOLESTERYL ESTER TRANSFER ACTIVITY

The purpose of this study was to determine if lipid transfer protein ( LTP I) regulates the plasma lipoprotein distribution of cyclosporine ( CSA). Experimental strategies that involved the supplementation and in hibition of LTP I were used to test these hypotheses. Incubation of CS A with human plasma supplemented with exogenous LTP I resulted in a si gnificantly greater percentage of CSA recovered in the high-density li poprotein (HDL)/lipoprotein deficient plasma (LPDP) fraction than in t he low-density lipoprotein (LDL)/very low-density lipoprotein (VLDL) f raction compared to plasma which had no exogenous LTP I added. incubat ion of radiolabeled cholesteryl ester (CE) or CSA-enriched HDL or LDL in T150 buffer supplemented with LTP I resulted in a significantly gre ater percentage of CE than CSA being transferred from HDL to LDL and L DL to HDL. However, the percent transfer from LDL to HDL was significa ntly lower for CE than CSA when these particles were incubated in LPDP that contained endogenous LTP I. The percent transfer of CE from HDL to LDL and LDL to HDL was significantly decreased in the presence of T P2, a monoclonal antibody directed against LTP I, compared to controls . The percent transfer of CSA from LDL to HDL was significantly decrea sed in the presence of TP2. However, the percent transfer of CSA from HDL to LDL in the presence of TP2 was not significantly different comp ared to controls. These findings suggest that the transfer of CSA betw een HDL and LDL is only partially facilitated through LIP I CE transfe r activity.