Modification of LDL by platelet secretory products induces enhanced uptake and cholesterol accumulation in macrophages.
LDL modified by incubation with platelet secretory products caused cholesterol accumulation and stimulation of cholesterol esterification in mouse peritoneal macrophages. Its uptake by the macrophages was a receptor-mediated process, not susceptible to competition by acetyl-LDL or polyanions suggesting independence of the scavenger receptor. Stimulation of the esterification process in macrophages by this modified LDL was inhibited by the lysosomal inhibitor chloroquine, indicating requirement for cellular uptake and lysosomal hydrolysis of the lipoprotein. Within the cell, the modified LDL inhibited cellular biosynthesis of triglycerides in a manner similar to the action of acetyl-LDL but different to the effect of native LDL. In the presence of HDL, acting in the medium as an acceptor for cholesterol, a low rate of cholesterol efflux from cells incubated with this modified LDL as well as with acetyl-LDL was demonstrated. A small reduction in cholesteryl ester synthesis was found in these cells, compared to a 60% reduction in cells incubated with native LDL. Thus it was demonstrated that LDL modified by platelet secretory products could induce macrophage cholesterol accumulation even though it was recognized and taken up via the regulatory LDL receptor.
Lipid Research Unit, Rambam Medical Center, Haifa, Israel.
B
B
Fuhrman
I
I
Maor
M
M
Rosenblat
G
G
Dankner
M
M
Aviram
J G
JG
Brook
D000328:Adult; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004951:Esterification; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D010529:Peritoneal Cavity; D014280:Triglycerides / Q000096:biosynthesis
D003470:Culture Media; D008077:Lipoproteins, LDL; D014280:Triglycerides; D002738:Chloroquine; D002784:Cholesterol