Uptake and processing of remnants of chylomicrons and very low density lipoproteins by rat liver.

In the rat, chylomicron remnants and very low density lipoprotein (VLDL) remnants are taken up into the liver by high affinity processes and appear to undergo degradation by lysosomes. The relationship of this catabolic process to the known pathways of uptake and degradation of low density lipoproteins (LDL) and the involvement of nonparenchymal cells are addressed in these studies. We have utilized both light and electron microscopic radioautography to determine whether the pathway of intracellular transport and catabolism resembles that established for LDL in hepatocytes. Radioiodinated plasma VLDL remnants and lymph chylomicron remnants were injected into femoral veins of rats and the livers were fixed by perfusion 3 to 30 minutes later. Quantitative light microscopic radioautography showed little or no accumulation of grains over Kupffer cells. Electromicroscopic radioautography confirmed these observations and, in addition, demonstrated that very few grains were associated with endothelial cells. The processing of the remnant particles closely resembled that of LDL. Following an initial association of grains with the parenchymal cell plasma membrane, frequently in regions in close proximity to clathrin-coated endocytic pits, the grains were found in endocytic vesicles just beneath the plasma membrane. By 15 minutes the grains were found over multivesicular bodies located in the Golgi-lysosome region of the cell. Thirty minutes after injection, radioautographic grains began to be associated with secondary lysosomes. These data indicate no significant role for nonparenchymal cells in the internalization and subsequent degradation of triglyceride-rich lipoproteins, and provide evidence that the processing of remnants as well as LDL follows the classical pathway of receptor-mediated endocytosis.