Cellular cholesterol regulates expression of the macrophage type B scavenger receptor, CD36

CD36, the macrophage type B scavenger receptor, binds and internalizes oxid ized low density lipoprotein (OxLDL), and may potentially play a role in th e development of atherosclerosis, We reported that the native and modified low density lipoproteins increased CD36 mRNA and protein (J. Biol, Chem, 27 2: 21654-21659), In this study, we investigated the effect of alterations o f cellular cholesterol content on macrophage expression of CD36, Depletion of cholesterol by treatment with beta-cyclodextrins (beta-cyclodextrin [bet a-CD] and methylated beta-cyclodextrin [Me beta CD]) significantly decrease d CD36 mRNA and I-125-labeled OxLDL binding, Conversely, loading macrophage s with cholesterol or cholesteryl ester (acetate) with Me beta CD:cholester ol complexes increased CD36 mRNA,I-125-labeled OxLDL binding, and CD36 surf ace expression as determined by fluorescence activated cell sorting. Thus, CD36 expression paralleled cellular cholesterol levels after removal of cho lesterol with beta-cyclodextrins or addition of cholesterol with Me beta CD :cholesterol complexes. Neither cholesterol depletion nor loading altered e xpression of type A scavenger receptor mRNA, Kinetics studies showed that c hanges in CD36 mRNA occurred after changes of cellular cholesterol, Neither beta-cyclodextrins nor Me beta CD:cholesterol altered CD36 mRNA half-life in the presence of actinomycin D, suggesting that alterations in CD36 expre ssion by cholesterol occur at the transcriptional level. These experiments demonstrate that CD36 expression is enhanced by cholesterol and down-regula ted by cholesterol efflux, and imply that macrophage expression of CD36 and foam cell formation in atherosclerotic lesions may be perpetuated by a cyc le in which lipids drive expression of CD36 in a self-regulatory manner.