Selective hepatic uptake of human β-hexosaminidase A by a specific glycoprotein recognition system on sinusoidal cells

C. J. Steer, J. W. Kusiak, R. O. Brady, E. A. Jones

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Intravenously administered 125I-labeled human β-hexosaminidase A (β-N-acetylglucosaminidase; 2-acetamido-2-deoxy-β-D-glucoside acetamidodeoxyglucohydrolase, EC 3.2.1.30) was rapidly cleared from the circulation of rats and accumulated in the liver. When hepatic cells were subsequently isolted, the label was recovered from both sinusoidal cells and, to a lesser extent, hepatocytes. Clearance was inhibited by the simultaneous infusion of mannan but not by a galactose-terminated glycoprotein. Studies in vitro, in which 125I-β-hexosaminidase was incubated with isolated hepatic cells, detected no uptake of the labeled ligand by hepatocytes. In contrast, uptake by sinusoidal cells was shown to be temperature dependent and approached saturability. Prior treatment of sinusoidal cells with Pronase resulted in markedly decreased uptake of 125I-β-hexosaminidase by these cells. Mannan and partially deglycosylated glycoproteins bearing terminal nonreducing N-acetylglucosamine or mannose residues were shown to be potent inhibitors of the cellular uptake of 125I-β-hexosaminidase; native orosomucoid and desialylated (galactoseterminated) orosomucoid were not inhibitory. Of six simple sugars tested, including N-acetylglucosamine, or mannose was an effective inhibitor of the cellular uptake of 125I-β-hexosaminidase. The kinetics of uptake of β-hexosaminidase and mannose-terminated orosomucoid by sinusoidal cells were shown to be similar. These findings suggest that the hepatic uptake of the lysosomal glycosidase β-hexosaminidase A is mediated by a receptor on sinusoidal cells which recognizes and binds mannose-terminated glycoproteins.

Original languageEnglish (US)
Pages (from-to)2774-2778
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume76
Issue number6
DOIs
StatePublished - 1979

Fingerprint Dive into the research topics of 'Selective hepatic uptake of human β-hexosaminidase A by a specific glycoprotein recognition system on sinusoidal cells'. Together they form a unique fingerprint.

Cite this