Efflux of lipid from macrophages after induction of lipid accumulation by chylomicron remnants.
The fate of cholesterol and triacylglycerol taken up and accumulated by macrophages after exposure to chylomicron remnants was investigated using macrophages derived from the human monocyte cell line THP-1 and chylomicron remnant-like particles containing human apolipoprotein (apo) E (CRLPs) as the experimental model. In THP-1 macrophages lipid loaded with CRLPs and incubated with various cholesterol acceptors for 24 h, the mass of cholesterol and cholesteryl ester found in the cells was not changed by HDL, HDL3 or lipid-free ApoA-I, although it was decreased by 38% by ApoA-I-phosphatidylcholine vesicles (ApoA-I-PC). After loading of the macrophages with [3H]cholesterol-labelled CRLPs, only about 5% of the label was effluxed in 24 h in the absence of cholesterol acceptors, and this increased to about 10% with ApoA-I or PC only, and to about 30% with apoA-I-PC. In similar experiments with [3H]triolein, only about 4% of the labelled triacylglycerol taken up by the cells was released into the medium in 24 h, and a large (>60%) and consistent proportion of the intracellular radioactivity remained associated with the triacylglycerol throughout this period. These results suggest that cholesterol and triacylglycerol derived from chylomicron remnants are not readily cleared from macrophages, and this is likely to contribute to the atherogenicity of the remnant lipoproteins.
Moore
Elizabeth H
EH
Department of Veterinary Basic Sciences, The Royal Veterinary College, Royal College Street, London NW1 0TU, UK.
Bejta
Fatos
F
Avella
Michael
M
Suckling
Keith E
KE
Botham
Kathleen M
KM
D000818:Animals; D015703:Antigens, CD; D001692:Biological Transport / Q000187:drug effects; D002417:Cattle; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D053298:Chylomicron Remnants; D002914:Chylomicrons / Q000494:pharmacology*; D006801:Humans; D007456:Iodine Isotopes; D050356:Lipid Metabolism; D051907:Lysosomal Membrane Proteins; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D010316:Particle Size; D011851:Radioactivity; D014280:Triglycerides / Q000378:metabolism
D015703:Antigens, CD; D053298:Chylomicron Remnants; D002914:Chylomicrons; D007456:Iodine Isotopes; D051907:Lysosomal Membrane Proteins; D014280:Triglycerides; D002784:Cholesterol