Metabolism of glycosylated human salivary amylase: in vivo plasma clearance by rat hepatic endothelial cells and in vitro receptor mediated pinocytosis by rat macrophages.
Salivary-type amylase normally comprises about 60% of the amylase activity in human serum, but only a small fraction is a glycosylated isoenzyme (amylase A). In contrast, 1/3 of amylase in human saliva is glycosylated. Since glycosylation can affect circulatory clearance, we studied the clearance of amylase A in rats and its uptake by rat alveolar macrophages. Following intravenous injection, 125I-labeled amylase A disappeared rapidly from plasma (t 1/2 = 9 min) and accumulated in the liver. Simultaneous injection of mannose-albumin slowed its clearance to a rate comparable to that of 125I-labeled nonglycosylated salivary amylase (t 1/2 = 45 min). In contrast, galactose-albumin had no effect. Electron microscope autoradiography of the liver following injection of 125I-labeled amylase A revealed a localization of grains over the hepatic endothelial cells. In vitro studies indicated that amylase A is taken up by alveolar macrophages via receptor-mediated pinocytosis. Uptake was linear over time, saturable, and inhibited by mannan and mannose-albumin, but not by galactose-albumin. We conclude that amylase A, which is a naturally occurring human glycoprotein with at most three terminal L-fucose residues per molecule, is recognized in rats by a mannose receptor located on hepatic endothelial cells. We speculate that this receptor, by rapidly clearing circulating amylase A, may be responsible for the low level of amylase A in human serum.
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001692:Biological Transport; D004727:Endothelium / Q000378:metabolism; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D037181:Lectins, C-Type; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008854:Microscopy, Electron; D010873:Pinocytosis; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000378:metabolism*; D012463:Saliva / Q000201:enzymology*
D007457:Iodine Radioisotopes; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000681:Amylases