Glycoproteins - Hughes, R. 1985

Functions
Catabolism and Clearance
Cells

The mammalian hepatocyte receptor apparently plays a role in determining the fate not only of soluble serum Glycoproteins, but also of circulating Cells, as it is capable of agglutinating erythrocytes. As shown in Chapter 2, the human erythrocyte membrane contains Glycophorin, the major glycoprotein of these membranes, which is rich in terminal sialic acid residues. Similar Proteins have been found On the surface of erythrocytes in most animal species. If radiolabeled erythrocytes are treated with neuraminidase and injected into the bloodstream of rats, rabbits, or dogs, The Cell-associated radioactivity rapidly disappears from the Blood and accumulates in the Liver or Spleen. In contrast, untreated cells are significantly more stable [79]. However, existing evidence argues against the involvement of the same hepatocyte receptor in the clearance of both Soluble Glycoproteins and erythrocytes. First, treating desialylated glycoproteins (such as ceruloplasmin) with galactose oxidase to convert the C-6 atom of terminal residues into aldehyde groups prevents protein clearance. The modified protein persists in the blood just as long as the control protein bearing terminal sialic acid. Evidently, the hepatocyte asialoglycoprotein receptor requires an intact primary hydroxyl group at C-6. Conversely, galactose oxidase Treatment of desialylated erythrocytes does not prolong their short Circulation half-life. Second, desialylated erythrocytes do not bind to isolated hepatocytes, but they bind strongly to Kupffer cells and mononuclear Cells of the spleen. This macrophage binding is inhibited by galactose. This suggests the existence of another carbohydrate-recognition system involved in the clearance of desialylated erythrocytes, which appears to be distinct from the hepatocyte receptor for terminal galactose-bearing glycoproteins [80].

All of these intriguing findings can be readily explained by the respective binding specificities of the galactose-inhibitable Lectins found on hepatocytes and Kupffer cells. The major sialylated glycoprotein of human Erythrocyte membranes—glycoprotein glycophorin—differs, for instance, from most serum glycoproteins by possessing an N-acetylglucosamine linked to the central core β-mannose residue. This structural feature likely dictates the preferential uptake of desialylated erythrocytes by Kupffer cells rather than hepatocytes, even though terminal galactose serves as the primary sugar recognized by both systems [81].

Untreated erythrocytes drawn from a normal blood sample are progressively cleared from the circulation. Erythrocytes of varying ages exhibit subtle differences in carbohydrate Structure; for instance, older cells contain 10–15% less sialic acid than newly formed ones. Since erythrocyte turnover is a continuous physiological process, it is highly probable that the phenomena observed in these experiments reflect the physiological mechanism governing the lifespan of red Blood Cells in the circulation.