title: Differential effect of subspecies of lipoprotein containing apolipoprotein A-I on cholesterol efflux from cholesterol-loaded macrophages: functional correlation with lecithin: cholesterol acyltransferase.
abstract: Two species of lipoprotein containing apoA-I, one containing only apoA-I (LpA-I), and the other containing apoA-I and apoA-II (LpA-I/A-II), were tested for their effects on macrophage foam cells. Rat macrophages were converted to foam cells by incubation with radiolabeled acetylated LDL. Incubation with LpA-I or LpA-I/A-II decreased the cellular cholesteryl esters (CE) mass. However, the free cholesterol (FC) mass was only reduced by LpA-I. All the radioactivity excreted into the medium was associated with LpA-I or LpA-I/A-II; 39% of the excreted radioactivity was esterified in LpA-I and 10% in LpA-I/A-II. Upon complete inactivation of lecithin: cholesterol acyltransferase (LCAT) activity with dithiobisnitrobenzoic acid, the cholesterol reducing capacity of LpA-I was weakened significantly. However, the CE mass reducing capacity of LpA-I/A-II was not affected. When LpA-I and LpA-I/A-II were combined, the cholesterol reducing capacity of the mixture was similar to that of LpA-I alone. However, LpA-I re-isolated from the medium showed a lower esterification rate than did the re-isolated LpA-I/A-II, thereby indicating that the cholesterol esterified in LpA-I was transferred to LpA-I/A-II. These results suggest that (i) the function of LpA-I is closely linked to the LCAT activity while that of LpA-I/A-II is not, and (ii) LpA-I in concert with LpA-I/A-II induces a series of extracellular events; LCAT-mediated esterification of excreted FC by LpA-I and a subsequent CE transfer to LpA-I/A-II. These mechanisms might be important for net cholesterol efflux from macrophage foam cells in physiological states.
authors.affiliation: Department of Pediatrics, Kumamoto University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohta
authors.forename: R
authors.initials: R
authors.lastname: Nakamura
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: M
authors.initials: M
authors.lastname: Shinohara
authors.forename: A
authors.initials: A
authors.lastname: Miyazaki
authors.forename: S
authors.initials: S
authors.lastname: Horiuchi
authors.forename: I
authors.initials: I
authors.lastname: Matsuda
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D016633:Apolipoprotein A-II / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D003470:Culture Media; D004591:Electrophoresis, Polyacrylamide Gel; D004951:Esterification; D005260:Female; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000737:chemistry / Q000201:enzymology*; D008297:Male; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*; D011851:Radioactivity; D051381:Rats; D017208:Rats, Wistar; D014461:Ultracentrifugation
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D003470:Culture Media; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase