Lysosomal and endosomal heterogeneity in the liver: A comparison of the intracellular pathways of endocytosis in rat liver cells

Abstract

Air-filled albumin microspheres, asialoorosomucoid and formaldehyde-treated serum albumin are selectively taken up by endocytosis in rat liver Kupffer cells, parenchymal cells and endothelial cells, respectively. Intracellular transport and degradation of endocytosed material were studied by subcellular fractionation in sucrose and Nycodenz gradients after intravenous injection of the ligand. By using ligands labeled with 125I-tyramine-cellobiose, the subcellular distribution of labeled degradation products can be studied because they are trapped at the site of formation. The results show that the kinetics of intracellular transport are different in hepatic parenchymal, endothelial and Kupffer cells. In endothelial cells, the ligand is associated with two types of endosomes during the first minutes after internalization and then is transferred rapidly to the lysosomes. In parenchymal cells, 125I-tyramine-cellobiose-asialoorosomucoid was located in a relatively slowly sedimenting vesicle during the first minute after internalization and subsequently in denser endosomes. Degradation of 125I-tyramine-cellobiose-asialoorosomucoid in parenchymal cells started later than that of 125I-tyramine-cellobiose-formaldehyde-treated serum albumin in endothelial cells. Furthermore, the ligand seemed to be transferred relatively slowly from endosomes to lysosomes, and most of the undegraded ligand was in the endosomes. The rate-limiting step of proteolysis in parenchymal cells is probably the transport from endosomes to lysosomes. In Kupffer cells, most 125I-tyramine-cellobiose-microspheres are found as undegraded material in very dense endosomes up to 3 hr after injection. After 20 hr, most of the ligand is degraded in lysosomes distributed at a lower density than the endosomes in Nycodenz and sucrose gradients.

Changes in receptor‐mediated endocytosis in liver sinusoidal cells after partial hepatectomy in the rat

“…The liver endothelial cells also perform an important homeostatic function by removing macromolecules from the circulation, and, recently, increased attention has been paid to these cells (3). Studies of the mechanism of endocytosis and intracellular degradation of fBSA have reported that fBSA is taken up via scavenger receptors on the endothelial cells (10)(11)(12)(13). Using fBSA, we tried to clarify the changes in endocytotic function of sinusoidal cells during liver regeneration.…”

“…However, changes in receptor-mediated endocytosis in sinusoidal cells during liver regeneration have not been much studied. To elucidate these changes in receptor-mediated endocytosis and to evaluate the functional recovery of sinusoidal cells after partial hepatectomy, we measured receptor-mediated en-docytosis in two-thirds hepatectomized rats using formaldehyde-treated bovine serum albumin, which is endocytosed via scavenger receptors on the sinusoidal cells (10)(11)(12)(13), as an endocytable macromolecule. Receptor-mediated endocytosis in hepatocytes was also measured using asialofetuin, which in mainly taken up by hepatocytes (14,15), and the changes in endocytotic function in sinusoidal cells were compared with that of hepatocytes.…”