title: Apolipoprotein A-I promotes cholesterol release and apolipoprotein E recruitment from THP-1 macrophage-like foam cells.
abstract: Apolipoprotein E (apoE) is synthesized and secreted by arterial macrophages while apolipoprotein A-I (apoA-I) is present in surrounding interstitial fluids. Both apolipoproteins play important roles in macrophage cholesterol homeostasis by forming lipid complexes (nascent-HDL) with cellular phospholipids (PL) and cholesterol (UC) thereby promoting cholesterol efflux. In this study, we evaluated the relative contributions of apoA-I and endogenously produced apoE in mediating the recruitment of cellular cholesterol. THP-1 human monocytes were differentiated (300 nm phorbol dibutyrate) into macrophages and macrophage-foam cells were generated by cholesterol loading with acetylated LDL (50 microg protein/ml). ApoA-I (10 microg/ml) depleted macrophage-foam cell cholesteryl esters by 50% in 24 h. This reduction was accompanied 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 macrophages (UC/PL = 0.59 +/- 0.08). Significantly more (70%) nascent-HDL were formed in incubations of apoA-I with macrophage-foam cells than with macrophages. Medium apoE accumulation paralleled the assembly of apoA-I containing nascent HDL where 2- and 4-fold increases were observed with macrophages and macrophage-foam cells, respectively, compared to incubations in the absence 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 macrophage-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 particles (19-20 nm). The predominance of apoA-I only particles indicates, however, that the assembly of apoA-I-containing nascent-HDL represents a major metabolic pathway of cellular cholesterol recruitment compared to the endogenous production of apoE.
authors.affiliation: Ernest Orlando Lawrence Berkeley National Laboratory, Life Sciences Division 1-213, University of California, Berkeley CA 94720, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Bielicki
authors.forename: M R
authors.initials: MR
authors.lastname: McCall
authors.forename: T M
authors.initials: TM
authors.lastname: Forte
mesh_terms: D016632:Apolipoprotein A-I / Q000378:metabolism / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D017077:Culture Media, Conditioned; D005487:Foam Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010316:Particle Size; D010743:Phospholipids / Q000032:analysis / Q000145:classification / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D002788:Cholesterol Esters; D017077:Culture Media, Conditioned; D008075:Lipoproteins, HDL; D010743:Phospholipids; D002784:Cholesterol