Evidence is presented suggesting that hepatocytes contain a receptor that binds glycoproteins specifically through fucose in al-..3 linkage to N-acetylglucosamine. Human After the initial observations of Ashwell and coworkers (1, 2) that mammalian hepatocytes contain a protein that specifically binds asialoglycoproteins through exposed galactose residues, several other animal binding proteins were reported. A (3-galactoside binding protein has been described from calf heart and lung (3), chick embryo thigh muscle (4), and the electric organ of Electrophorus electricus (5), but they have properties that differ somewhat from the hepatocyte protein and perhaps from one another. Avian liver also contains a protein that binds glycoproteins with exposed N-acetylglucosamine (6), and considerable evidence has been reported for mannose-specific binding proteins (7).This report provides evidence suggesting the presence of a receptor in hepatocytes that specifically binds oligosaccharides in glycoproteins through a fucosyl al-3 N-acetylglucosamine group. These studies were prompted by the observations that human lactoferrin (Lf) was rapidly cleared from the circulation when injected intravenously in rats and mice, and that over 90% of the injected protein was recovered in hepatocytes.The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement " in accordance with 18 U. S. C. §1734 solely to indicate this fact.Much is known about Lf structure although its biological role is obscure (8). Lf, like serotransferrin (Tf), has two iron-binding sites, and iron binding is dependent on bicarbonate (9). Its amino acid sequence is homologous with that of Tf (10, 11) and ovotransferrin (11) and it contains two oligosaccharide chains, which are structurally similar to those of serotransferrin ( Fig. 1), except that additional fucose residues are in a1->3 linkage with the N-acetylglucosamine residues adjacent to galactose and those chains containing fucose are devoid of sialic acid (11, 12, and unpublished observations

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The binding of several glycoproteins to freshly grown and harvested cells of Mycoplasma gallisepticum was examined. Only human glycophorin, the major sialoglycoprotein of the erythrocyte membrane, bound tightly as judged by direct binding assays with 125I-labeled glycoproteins. Neuraminidase-treated glycophorin did not bind, suggesting that binding is mediated through sialic acid groups. Although other sialoglycoproteins did not appear to bind M. gallisepticum by direct binding assays, some inhibited the binding of glycophorin. The best inhibitors had a mucin-like structure, with high molecular weights and high sialic acid contents. N-acetylneuraminic acid appeared to be the favored sialic acid structure for binding, but there was no strict specificity for its anomeric linkage. Neuraminidase activity could not be detected on the surface of M. gallisepticum, suggesting that this enzyme is not involved in the mechanism of adherence of sialoglycoproteins. Binding of sialoglycoproteins was time dependent, however, and markedly diminished with increasing ionic strength, but was largely unaffected between pH 4 and 9.