Morphological Characterization of Scavenger Receptor-Mediated Processing of Modified Lipoproteins by Rat Liver Endothelial Cells

SummaryExperiments were carried out to charact erize the specificity of uptake of tPA in rat liver cells. Endocytosis in liver endothelial cells of the native carbohydrate variants of tissue plasminogen activator (tPA), and tPA inactivated by diisopropyl fluorophosphate was found to be competitive, suggesting that the determinant being recognized by these cells is different from the active site. Fibronectin and urokinase, which show partial homology with tPA, did not compete with tPA for uptake in liver endothelial cells. Hyaluronic acid, collagen, or IgG, which are endocytosed by specific receptors in liver endothelial cells, did not interfere with the uptake.Reduced endocytosis by liver endothelial cells was observed with tPA modified in the carbohydrate side chains, suggesting that these structures are important for uptake. Ovalbumin, mannan, mannose, fructose, and EDTA, but not galactose, effectively inhibited uptake in liver endothelial cells of both native and diisopropyl fluorophosphate-inhibited tPA, but had very little effect on the uptake of tPA modified in the carbohydrate side chains.Endocytosis of native tPA by parenchymal cells could be inhibited by galactose, ovalbumin, and EDTA, but not by mannose.These results suggest that endocytosis of tPA by liver endothelial cells and parenchymal cells is mediated by the mannose and galactose receptors, respectively.

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Uptake and Degradation of Tissue Plasminogen Activator in Rat Liver

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647518 ◽

1988 ◽

Vol 59 (03) ◽

pp. 474-479 ◽

Cited By ~ 35

Author(s):

Monica Einarsson ◽

Bård Smedsrød ◽

Håkan Pertoft

Keyword(s):

Endothelial Cells ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Rat Liver ◽

Liver Cells ◽

Terminal Phase ◽

Tissue Plasminogen ◽

Liver Endothelial Cells ◽

Parenchymal Cells

SummaryThe mechanism of uptake of tissue plasminogen activator (tPA) in rat liver was studied. Radio-iodinated tPA was removed from the circulation after intravenous administration in a biphasic mode. The initial half life, t1/2(α), and the terminal phase, t1/2(β), were determined to be 0.5 min and 7.5 min, resp. Separation of the liver cells by collagenase perfusion and density centrifugation, revealed that the uptake per cell was two to three times higher in the non-parenchymal cells than in the parenchymal cells.Endocytosis of fluorescein isothiocyanate-labelled or 125I-labelled tPA was studied in pure cultures of liver cells in vitro. Liver endothelial cells and parenchymal cells took up and degraded tPA. Endocytosis was more efficient in liver endothelial cells than in parenchymal cells, and was almost absent in Kupffer cells.Competitivb inhibition experiments showing that excess unlabelled tPA could compete with the uptake and degradation of 125I-tPA, suggested that liver endothelial cells and parenchymal cells interact with the activator in a specific manner. Endocytosis of trace amounts of 125I-tPA in cultures of liver endothelial cells and parenchymal cells was inhibited by 50% in the presence of 19 nM unlabelled tPA. Agents that interfere with one or several steps of the endocytic machinery inhibited uptake and degradation of 125I-tPA in both cell types.These findings suggest that 1) liver endothelial cells and parenchymal cells are responsible for the rapid hepatic clearance of intravenously administered tPA; 2) the activator is taken up in these cells by specific endocytosis, and 3) endocytosed tPA is transported to the lysosomes where it is degraded.

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Endocytosis of formaldehyde-treated serum albumin via scavenger pathway in liver endothelial cells

Biochemical Journal ◽

10.1042/bj2180081 ◽

1984 ◽

Vol 218 (1) ◽

pp. 81-86 ◽

Cited By ~ 72

Author(s):

R Blomhoff ◽

W Eskild ◽

T Berg

Keyword(s):

Endothelial Cells ◽

Low Density Lipoprotein ◽

Scavenger Receptor ◽

Density Lipoprotein ◽

Low Density ◽

Surface Culture ◽

Rat Liver Cells ◽

Liver Endothelial Cells ◽

Isolated Liver

Denatured or modified proteins (including albumin and low-density lipoprotein) are catabolized in vitro via scavenger receptors. We have studied the distribution of formaldehyde-denatured albumin in rat liver cells after intravenous injection of tracer doses of the protein. At 12 min after injection, most of the formaldehyde-denatured albumin (about 70% of the injected dose) was recovered in liver endothelial cells. Furthermore, isolated liver endothelial cells in suspension and in surface culture took up formaldehyde-denatured albumin by receptor-mediated endocytosis. Our data indicate that the scavenger receptor in liver is mainly located on the endothelial cells. Implications for the catabolism of low-density lipoproteins are discussed.

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