The effect of α-mannose-terminal oligosaccharides on the survival of glycoproteins in the circulation: Rapid uptake and catabolism of bovine pancreatic ribonuclease B by nonparenchymal cells of rat liver

Abstract

125 I-Labeled ribonuclease B (RNase B), injected intravenously, is rapidly cleared from the rat circulation ( t 12 ∼ 15 min). Clearance of this glycoprotein depends on specific recognition of the α-mannosyl residues of the attached oligosaccharide and is inhibited by the coinjection of an excess of unlabeled RNase B or yeast mannan, but not by RNase A, dextrans, galactan, or asialofetuin. Following 125 I-labeled RNase B injection into nephrectomized rats, radioactivity accumulated primarily in the lysosomal subcellular fraction in the liver and was rapidly degraded to low molecular weight iodinated products. Free iodide began to accumulate in the stomach and intestines after 30 min. Liver, spleen, and bone marrow were most active, on a weight basis, in the clearance of RNase B. At 15 min after the injection of 125 I-labeled RNase B, parenchymal and nonparenchymal cells were isolated from liver following perfusion with dilute formalin and collagenase. More than 90% of the radioactivity was localized in the nonparenchymal cell fraction. The evidence indicates that mannose-dependent glycoprotein clearance from the circulation occurs primarily in tissues characteristic of the reticuloendothelial system.