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

Abstract

CD36, the macrophage type B scavenger receptor, binds and internalizes oxidized low density lipoprotein (OxLDL), and may potentially play a role in the development of atherosclerosis. We reported that the native and modified low density lipoproteins increased CD36 mRNA and protein (J. Biol. Chem. 272: 21654–21659). In this study, we investigated the effect of alterations of cellular cholesterol content on macrophage expression of CD36. Depletion of cholesterol by treatment with β-cyclodextrins (β-cyclodextrin [β-CD] and methylated β-cyclodextrin [MeβCD]) significantly decreased CD36 mRNA and 125I-labeled OxLDL binding. Conversely, loading macrophages with cholesterol or cholesteryl ester (acetate) with MeβCD:cholesterol complexes increased CD36 mRNA, 125I-labeled OxLDL binding, and CD36 surface expression as determined by fluorescence activated cell sorting. Thus, CD36 expression paralleled cellular cholesterol levels after removal of cholesterol with β-cyclodextrins or addition of cholesterol with MeβCD:cholesterol complexes. Neither cholesterol depletion nor loading altered expression of type A scavenger receptor mRNA. Kinetics studies showed that changes in CD36 mRNA occurred after changes of cellular cholesterol. Neither β-cyclodextrins nor MeβCD:cholesterol altered CD36 mRNA half-life in the presence of actinomycin D, suggesting that alterations in CD36 expression by cholesterol occur at the transcriptional level. These experiments demonstrate that CD36 expression is enhanced by cholesterol and down-regulated by cholesterol efflux, and imply that macrophage expression of CD36 and foam cell formation in atherosclerotic lesions may be perpetuated by a cycle in which lipids drive expression of CD36 in a self-regulatory manner.—Han, J., D. P. Hajjar, J. M. Tauras, and A. C. Nicholson. Cellular cholesterol regulates expression of the macrophage type B scavenger receptor, CD36. J. Lipid Res. 1999. 40: 830–838.