In Vivo Regulation of Scavenger Receptor BI and the Selective Uptake of High Density Lipoprotein Cholesteryl Esters in Rat Liver Parenchymal and Kupffer Cells

High density lipoprotein cholesteryl esters (HDL-CE) are selectively taken up by liver parenchymal cells without parallel apolipoprotein uptake. This selective uptake route forms an important step in the so-called reverse cholesterol transport. Scavenger receptor BI (SR-BI) is the only known HDL receptor which can mediate selective uptake of HDL-CE. In the present study we investigated its regulation in liver cells. The down-regulation of SR-BI expression in liver by 17alpha-ethinyl estradiol (EE) treatment was found by immunoblotting to be the consequence of down-regulation of SR-BI in parenchymal cells, while SR-BI expression in Kupffer cells was up-regulated. The selective uptake of HDL-CE in vivo by parenchymal and Kupffer cells was measured by labeling of HDL with 3HCE and analysis of the cellular uptake at 10 min after injection. After EE treatment, uptake of 3HCE-labeled HDL by parenchymal cells decreased by 85%, while Kupffer cells showed a 4-fold increase in selective uptake of 3HCE-labeled HDL. In vitro studies with isolated parenchymal cells indicated that after EE treatment, the selective uptake of 3HCE labeled HDL was 3-4-fold lower, indicating that the in vivo observations are also reflected in vitro. A 2-week high-cholesterol diet leads to lowering of SR-BI expression in parenchymal cells, while the expression in Kupffer cells is increased. Like EE treatment, the selective uptake of 3HCE-labeled HDL by the two hepatic cell types in vivo correlated with the changes in expression of SR-BI. Our results thus demonstrate that within the liver, the regulation of SR-BI expression by EE treatment or a high-cholesterol diet, correlates with changes in the selective uptake of HDL-CE, supporting a function of SR-BI to mediate the selective uptake of HDL-CE in the liver parenchymal cells. The contrasting regulatory effect on parenchymal cells and Kupffer cells might indicate a different function of SR-BI in the latter cell type.