Alpha-tocopherol down-regulates scavenger receptor activity in macrophages

The aim of this study was to investigate the effect of alpha-tocopherol on scavenger receptor (SR) activity, SR class A (SR-A) mRNA expression and transcriptional regulation in macrophages. Scavenger receptor activity was determined quantitatively by uptake of DiI-acLDL (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-labeled acetylated low-density lipoprotein) in rabbit peritoneal macrophages and human monocytes/macrophages in the presence and absence of different tocopherol homologues. SR-A mRNA expression was determined by Northern blotting, the activity of the transcription factor activator protein-1 (AP-1) by electrophoretic mobility shift assay. We could demonstrate that alpha-tocopherol down-regulates scavenger receptor activity in macrophages in a dose-dependent manner. Scavenger receptor activity was reduced by 13, 16, 18 and 24% in the presence of 1, 5, 10 and 50 microM alpha-tocopherol, respectively. This effect was associated with a reduced SR-A mRNA expression and activity of AP-1 binding transcription factors in the presence of alpha-tocopherol. The activity of scavenger receptors in human monocyte derived macrophages incubated with 100 microM alpha-tocopherol for 15 days was reduced up to 60%. Interestingly, gamma-tocopherol, which is a homologue of alpha-tocopherol with a comparable antioxidative capacity, showed only a weak suppression of SR activity, SR-A expression and AP-1 activity. Our observations point to the conclusion that the reduction of SR-A expression and activity in presence of alpha-tocopherol is possibly related to its direct action on cell signaling.