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

fl-Migrating very-low-density lipoprotein (fl-VLDL) is a cholesteryl-ester-enriched lipoprotein which under normal conditions is rapidly cleared by parenchymal liver cells. In this study the characteristics of the interaction of,6-VLDL with rat parenchymal cells, Hep G2 cells and human parenchymal cells are evaluated. The binding of fl-VLDL to these cells follows saturation kinetics (Bmax respectively 117, 106 and 103 ng of 8-VLDL apoliprotein/mg of cell protein), with a relatively high affinity (Kd respectively for 8-VLDL of 10.7, 5.1 and 8.4,ag/ml). Competition studies of unlabelled /3VLDL, low-density lipoprotein (LDL) or acetylated LDL with the binding of radiolabelled ,-VLDL indicate that a LDLreceptor-independent, Ca2+-independent, specific recognition site for ,-VLDL is present on rat and human parenchymal cells, whereas with Hep G2 cells or mouse macrophages /J-VLDL recognition is performed by the LDL receptor. The binding of/-VLDL to Hep G2 cells was down-regulated by 89 % by prolonged exposure to ,-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 fl-VLDL recognition site on rat and human parenchymal cells. It is concluded that a LDL-receptor-independent recognition site for ,6-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 fl-VLDL during consumption of a cholesterol-rich diet, when LDL receptors are down-regulated, thus protecting against the extrahepatic accumulation of the atherogenic 8-VLDL constituents.