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

Abstract

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 [3H]CE and analysis of the cellular uptake at 10 min after injection. After EE treatment, uptake of [3H]CE-labeled HDL by parenchymal cells decreased by 85%, while Kupffer cells showed a 4-fold increase in selective uptake of [3H]CE-labeled HDL. In vitro studies with isolated parenchymal cells indicated that after EE treatment, the selective uptake of [3H]CE 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 [3H]CE-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.