Intralipid infusion abolishes ability of human serum to cholesterol-load cultured macrophages.
Intralipid is widely used for intravenous alimentation and contains triglyceride-emulsion particles and phospholipid liposomes. After infusion, triglyceride-emulsion particles resemble chylomicron remnants and thus may be atherogenic. On the other hand, intravenous infusion of phospholipid liposomes produces regression of experimental atherosclerosis and abolishes the ability of hypercholesterolemic rabbit plasma to cholesterol-load cultured macrophage foam cells. To determine the net effect of intralipid infusion on cellular cholesterol balance, J-774 macrophages were incubated for 18 hours with human serum obtained before, during, and after a 6-hour infusion of 10% Intralipid. Compared to serum-free medium, pre-infusion serum increased cellular unesterified cholesterol by 76% and cholesteryl ester by 78%. In contrast, serum obtained after the 6-hour infusion reduced cellular unesterified cholesterol by 23% and cholesteryl ester by 15%. Serum obtained 18 hours after the end of the infusion still showed impaired cholesterol-loading ability. Mouse peritoneal macrophages incubated with these serum samples behaved similarly. Compared to pre-infusion serum, postinfusion serum inhibited cellular uptake of 125I-low density lipoprotein and 125I-very low density lipoprotein by 50% and 80%, respectively, and also enhanced the efflux of cellular cholesterol by 46%. We conclude that the ability of human serum to cause cholesterol accumulation in cultured macrophages is abolished by an infusion of Intralipid. This effect is mediated by a reduction in cholesterol uptake by the cells and by an increase in cell cholesterol efflux. If similar events occur in the arterial wall, Intralipid infusion might inhibit foam cell formation in vivo.
Aviram
M
M
Department of Pediatrics, College of Physicians and Surgeons of Columbia University.
Williams
K J
KJ
McIntosh
R A
RA
Carpentier
Y A
YA
Tall
A R
AR
Deckelbaum
R J
RJ
D000818:Animals; D001769:Blood; D002460:Cell Line; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D002788:Cholesterol Esters / Q000097:blood / Q000378:metabolism; D004655:Emulsions; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D010743:Phospholipids / Q000097:blood / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood / Q000494:pharmacology
D002788:Cholesterol Esters; D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D008055:Lipids; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D008081:Liposomes; D010743:Phospholipids; D014280:Triglycerides; D002784:Cholesterol