Apolipoprotein A-I promotes cholesterol release and apolipoprotein E recruitment from THP-1 macrophage-like foam cells

Apolipoprotein E (apoE) is synthesized and secreted by arterial macrophages while apolipoprotein A-I (apoA-I) is present in surrounding interstitial f luids. Both apolipoproteins play important roles in macrophage cholesterol homeostasis by forming lipid complexes (nascent-HDL) with cellular phosphol ipids (PL) and cholesterol (UC) thereby promoting cholesterol efflux, In th is study, we evaluated the relative contributions of apoA-I and endogenousl y produced apoE in mediating the recruitment of cellular cholesterol, THP-1 human monocytes were differentiated (300 nM phorbol dibutyrate) into macro phages and macrophage-foam cells were generated by cholesterol loading with acetylated LDL (50 mu g protein/ml), ApoA-I (10 mu g/ml) depleted macropha ge-foam cell cholesteryl esters by 50% in 24 h, This reduction was accompan ied by a significant increase in the UC/PL mole ratio of nascent HDL (UC/PL = 0.80 +/- 0.15) in the medium compared to complexes isolated from macroph ages (UC/PL = 0.59 +/- 0.08). Significantly more (70%) nascent-HDL were for med in incubations of apoA-I with macrophage-foam cells than with macrophag es. Medium apoE accumulation paralleled the assembly of apoA-I containing n ascent HDL where 2- and 4-fold increases were observed with macrophages and macrophage-foam cells, respectively, compared to incubations in the absenc e of apoA-I, Despite the increase in medium apoE accumulation, a majority ( 85%) of particles (11, 9, and 7.4 nm in diameter) from macrophages and macr ophage-foam cells possessed apoA-I without apoE, ApoA-I plus apoE particles (13-16 nm) were also formed along with a small quantity of apoE-only parti cles (19-20 nm). The predominance of apoA-I only particles indicates, howev er, that the assembly of apoA-I-containing nascent-HDL, represents a major metabolic pathway of cellular cholesterol recruitment compared to the endog enous production of apoE.