α-Tocopherol decreases CD36 expression in human monocyte-derived macrophages

Abstract

Cholesterol-laden macrophages are the hallmark of atherogenesis. The class B scavenger receptor, CD36, binds oxidized low density lipoprotein (OxLDL), is found in atherosclerotic lesions, and is upregulated by OxLDL. We tested the effects of a -tocopherol (AT) enrichment of hu- man monocyte-derived macrophages on CD36 expression and cholesteryl ester accumulation. Monocytes isolated from normal volunteers were cultured into macrophages. Macrophages were enriched overnight with various doses of AT (25, 50, and 100 m M). LDL from normal volunteers was oxidized or acetylated (AcLDL) and incubated with mac- rophages for 48 h at a concentration of 50 or 100 m g/ml. CD36 expression was assessed by flow cytometry. Quantita- tive analysis of scavenger receptor class A (SR-A) activity was performed with 1,1 9 -dioctadecyl-3,3,3 9 ,3 9 -tetramethylin- docarbocyanide perchlorate (DiI)-labeled LDL. CD36 ex- pression was maximal after 8-10 days of culture. AT ( > 50 m M) significantly decreased CD36 expression upregulated by OxLDL and AcLDL ( P , 0.01). Other antioxidants ( b - or g -tocopherol) or protein kinase C inhibitors failed to de- crease CD36 expression. Concomitantly, DiI-AcLDL and DiI-OxLDL uptake was significantly decreased after AT treatment ( P , 0.001). Cholesteryl ester accumulation was significantly decreased after AT enrichment (AcLDL 1 AT, 77% inhibition; OxLDL 1 AT, 42% inhibition). In conclu- sion, AT decreases both CD36 and SR-A expression and cholesteryl ester accumulation in human macrophages. This provides additional scientific support for the antiathero- genic properties of AT. — Devaraj, S., I. Hugou, and I. Jialal. a -Tocopherol decreases CD36 expression in human monocyte- derived macrophages. J. Lipid Res. 2001. 42: 521-527.