Unidirectional inhibition of lipid transfer protein I-mediated transfer of cholesteryl esters between high-density and low-density lipoproteins by amphotericin B lipid complex

Purpose. The purpose of this study was to determine whether Fungizone or amphotericin B lipid complex (ABLC; ABELCET(R)) affects the transfer of cholesteryl ester (CE) by lipid transfer protein I (LTP I; also known as cholesteryl ester transfer protein) between HDL and LDL (bidirectional transfer HDL to LDL and LDL to HDL). Methods. Increasing concentrations of either Fungizone or ABELCET(R) (1.25-12.5 mug AmpB/ml) were incubated with HDL and [3H]CE-LDL or [3H]CE-HDL and LDL (the amount of each fraction added was equivalent to 10 mug of cholesterol) and LTP I in delipidated human plasma at 37degreesC for 90 min. As a positive control, TP2, a monoclonal antibody directed against LTP-1, was added instead of drug. After incubation, manganese and phosphate reagents were then added to precipitate out all of the LDL. The supernatant, consisted of only HDL, was counted for radioactivity to determine the amount of CE transferred from LDL. Similarly, the precipitate consisted of only LDL, was counted for radioactivity to determine the amount of CE transferred from HDL. Results. For Fungizone, the transfer of cholesteryl ester (CE) between HDL and LDL were not significantly different compared to nontreated controls. For ABELCET(R), CE transfer from HDL to LDL was significantly decreased at 12.5 mug AmpB/ml compared to control. However, transfer from LDL to HDL was not significantly different compared to non-treated controls. Similar results were observed with the major lipid component of ABELCET(R), dimyristoylphosphatidylcholine. CE transfer from HDL to LDL and LDL to HDL was significantly decreased when using the positive control (TP2). Conclusions. Fungizone does not affect LTP I-mediated transfer of CE between HDL and LDL. ABELCET(R) inhibits transfer from HDL to LDL, but has no effect on CE transfer from LDL to HDL. This uni-directional inhibition may contribute to the high recovery of AmpB in HDL but the very low presence of drug in the LDL fraction following ABELCET(R) incubation.