Evidence for carbohydrate-independent endocytosis of tissue-type plasminogen activator by liver cells.
In the liver, tissue-type plasminogen activator (t-PA) is endocytosed by hepatic parenchymal (PC), endothelial (EC) and Kupffer (KC) cells. Although the endocytosis is receptor-mediated, it remains a matter of discussion which receptors are involved in this catabolic process. To evaluate the role of a protein-specific receptor, as well as the possible involvement of the galactose receptor on PC and the mannose receptor on EC, we have employed different glycosylation variants of t-PA in biochemical and immunocytochemical studies. Partial or total removal of carbohydrate side-chains by endoglycosidases did not prevent clearance and hepatic endocytosis of t-PA by either of the liver cell types. Blockade of the galactose and mannose receptors by co-application of a large excess of the glycoprotein ovalbumin remained without effect on the binding and uptake of t-PA by hepatic cells. However, the contribution of different liver cell types to the hepatic clearance of t-PA was to a certain extent dependent on the type of oligosaccharide chains removed. The mannose receptor on EC is partially responsible for the clearance of t-PA by this cell type, whereas the galactose receptor does not seem to be involved in this process. The results obtained in this study further demonstrate that the major portion of the hepatic catabolism of t-PA is independent of its carbohydrate side-chains.
Stang
E
E
Electronmicroscopical Unit for Biological Sciences, University of Oslo, Blindern, Norway.
Roos
N
N
Schlüter
M
M
Berg
T
T
Krause
J
J
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D002241:Carbohydrates / Q000502:physiology*; D004705:Endocytosis / Q000187:drug effects; D004727:Endothelium / Q000378:metabolism; D006031:Glycosylation; D006596:Hexosaminidases / Q000378:metabolism; D007150:Immunohistochemistry; D007700:Kinetics; D007728:Kupffer Cells / Q000378:metabolism; D037181:Lectins, C-Type; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D002241:Carbohydrates; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C039707:galactose receptor; D006596:Hexosaminidases; D010959:Tissue Plasminogen Activator; D000581:Amidohydrolases; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase