Characterization of the low-density-lipoprotein-receptor-independent interaction of β-very-low-density lipoprotein with rat and human parenchymal liver cells in vitro

Abstract

β-Migrating very-low-density lipoprotein (β-VLDL) is a cholesteryl-ester-enriched lipoprotein which under normal conditions is rapidly cleared by parenchymal liver cells. In this study the characteristics or the interaction of β-VLDL with rat parenchymal cells, Hep G2 cells and human parenchymal cells are evaluated. The binding of β-VLDL to these cells follows saturation kinetics (B(max) respectively 117, 106 and 103 ng of β-VLDL apoliprotein/mg of cell protein), with a relatively high affinity (K(d) respectively for β-VLDL of 10.7, 5.1 and 8.4 μg/ml). Competition studies of unlabelled β-VLDL, low-density lipoprotein (LDL) or acetylated LDL with the binding of radiolabelled β-VLDL indicate that a LDL-receptor-independent, Ca2+-independent, specific recognition site for β-VLDL is present on rat and human parenchymal cells, whereas with Hep G2 cells or mouse macrophages β-VLDL, recognition is performed by the LDL receptor. The binding of β-VLDL to Hep G2 cells was down-regulated by 89% by prolonged exposure to β-VLDL. whereas for human parenchymal and rat parenchymal cells down-regulation of 44% and 20% respectively was observed. Studies with antibodies against the LDL receptor support the presence of a LDL-receptor-independent specific β-VLDL recognition site on rat and human parenchymal cells. It is concluded that a LDL-receptor-independent recognition site for β-VLDL is present on rat and human parenchymal liver cells, The presence of a LDL-receptor-independent recognition site on human parenchymal cells may mediate in vivo the uptake of β-VLDL during consumption or a cholesterol-rich diet, when LDL receptors are down-regulated, thus protecting against the extrahepatic accumulation of the atherogenic β-VLDL constituents.