The effect of macrophage stimulation on the uptake of acetylated low-density lipoproteins.
The rapid uptake of modified low-density lipoproteins (LDL) by macrophages in the arterial wall may lead to their conversion into lipid-laded foam cells in atherosclerotic lesions. We have therefore investigated the effects of macrophage stimulation on their rate of uptake of modified LDL. The uptake of 125I-labelled acetyl-LDL by mouse resident peritoneal macrophages was reduced by about 60-85% by zymosan (250 micrograms/ml), by 25-45% by lipopolysaccharide (0.1-1 mg/ml) and 50-60% by phorbol myristate acetate (100 nM). The inhibition was dose-dependent and was observed at the earliest times studied (about 1 h). Binding studies at 0 degrees C showed that all three stimulating agents decreased the number of cell-surface receptors for acetyl-LDL. If macrophages are stimulated in atherosclerotic lesions, this may therefore be beneficial in that it may decrease their numbers of receptors for modified LDL, although it may be harmful in other ways in that stimulated macrophages may release factors that damage the arterial wall.
Leake
D S
DS
Pharmacology Group, King's College London, University of London, U.K.
May
G
G
Soyombo
A A
AA
Nasr-Esfahani
M H
MH
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; C032629:acetyl-LDL; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate