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

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 teste d the effects of or-tocopherol (AT) enrichment of human monocyte-derived ma crophages 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 muM). LD L from normal volunteers was oxidized or acetylated (AcLDL) and incubated w ith macrophages for 48 h at a concentration of 50 or 100 mug/ml. CD36 expre ssion was assessed by flow cytometry, Quantitative analysis of scavenger re ceptor class A (SR-A) activity was performed with 1,1'-dioctadecyl-3,3,3',3 '-tetramethylin docarbocyanide perchlorate (DiI)-labeled LDL, CD36 expressi on was maximal after 8-10 days of culture, AT (greater than or equal to 50 muM) significantly decreased CD36 expression upregulated by OxLDL and AcLDL (P < 0.01), Other antioxidants (<beta>- or gamma -tocopherol) or protein k inase C inhibitors failed to decrease CD36 expression, Concomitantly, DiI-A cLDL and DiI-OxLDL uptake was significantly decreased after AT treatment (P < 0.001), Cholesteryl ester accumulation was significantly decreased after AT enrichment (AcLDL + AT, 77% inhibition; OxLDL + AT, 42% inhibition). In conclusion, AT decreases both CD36 and SR-A expression and cholesteryl est er accumulation in human macrophages. This provides additional scientific s upport for the antiatherogenic properties of AT.