The mechanisms of cholesterol efflux from macrophages — the role of phospholipid transfer protein

Abstract

We studied the interaction of cholesterol-loaded macrophages with human phospholipid transfer protein
(PLTP). PLTP did not stimulate efflux of lipids (phospholipids and cholesterol) in the presence of albumin, purified
apolipoprotein A-I and phospholipid vesicles. PLTP restored lipids efflux as a result of mild trypsinization of high
density lipoproteins (HDL), presumably due to the generation of active apolipoproteins. Stimulated by PLTP lipids
efflux was absent in macrophages obtained from Tanger disease patients (during efflux induction by macrophage
cholesterol loading and inhibition by Brefeldin A), which indicates the selectivity of effect for the
apolipoprotein-mediated lipid efflux. The effect of PLTP on the lipids flow stimulation was not associated with the
generation of pre HDL particles in the solution, but needed interaction with macrophages. This interaction increases
cholesterol efflux carried out by minor HDL vesicles having the values of electrophoretic mobility between
the characteristics of -HDL and HDL-pre. These results indicate that PLTP promotes HDL binding to the cell surface
and remodeling of HDL in order to improve the capacity of HDL particles for induction cholesterol and
phospholipids efflux by apolipoprotein-mediated pathway.