Saturable high affinity binding, uptake and degradation of rat plasma lipoproteins by isolated parenchymal and non-parenchymal cells from rat liver

Abstract

1. Freshly isolated rat parenchymal and non-parenchymal liver cells bind iodinated rat very low density lipoprotein (VLDL) remnants, low density lipoproteins (LDL) and high density lipoproteins (HDL) in a saturable way. The apparent K m values for the binding of VLDL remnants are 6–20-fold lower than for LDL or HDL. The binding per mg cell protein to non-parenchymal cells is 5–8-fold higher than to parenchymal cells. Competition experiments indicate that rat VLDL-remnants, LDL and HDL, but not human LDL compete for the same surface receptor. It is concluded that the source of common recognition could be apolipoprotein E and that the interaction with the receptor is also influenced by the apolipoproteins A and C. The high apparent affinity of the receptor for VLDL remnants might be the result of multiple receptor occupancy of this lipoprotein. The presence of a 5–8-fold higher concentration of the described lipoprotein receptor in non-parenchymal cells as compared to parenchymal cells explains the relatively high uptake of VLDL remnants (as compared to LDL and HDL) as well as the relative contribution of parenchymal and non-parenchymal cells to the total hepatic uptake of lipoproteins in vivo. 2. The greater part (70–80%) of the parenchymal and non-parenchymal cell-associated apolipoproteins, LDL or HDL, remains bound to the external surface of the cells, during in vitro incubation at 37°C. High-affinity degradation of apolipoprotein(s) by isolated liver cells is dependent on the specific lipoprotein. During a 3 h incubation at 37°C, 37–49% of the total cell-associated 125I-abeled HDL is degraded. These percentages are 11–13% for 125I-labeled LDL and 4–8% for 125I-labeled VLDL remnants. Degradation of the different lipoproteins by non-parenchymal liver cells occurs at a 3–6-times higher rate per mg cell protein than by parenchymal cells. It is suggested that the rate-limiting step in the degradation of apolipoprotein by isolated liver cells is their transport to intracellular degradation sites.