Hepatic receptor that specifically binds oligosaccharides containing fucosyl α1→3 N -acetylglucosamine linkages

Publisher Website
Google Scholar
Abstract
Evidence is presented suggesting that hepatocytes contain a receptor that binds glycoproteins specifically through fucose in .alpha.1 .fwdarw. 3 linkage to N-acetylglucosamine. Human lactoferrin, which contains this type of linkage, is rapidly cleared from the circulation of mice after i.v. injection, and greater than 90% of the injected material is found in hepatocytes. Binding of lactoferrin is mediated through its carbohydrate groups, since its clearance is prolonged after periodate oxidation or after its oligosaccharide groups are extensively degraded with glycosidases. In addition, glycopeptides from lactoferrin inhibit lactoferrin clearance. That lactoferrin clearance is mediated through binding to its fucosyl groups is suggested for several reasons. Transferrin and asialotransferrin, whose oligosaccharide groups are essentially structurally identical to those of lactoferrin but devoid of fucose, are not cleared on i.v. injection. When fucose is incorporated into asialotransferrin by .alpha.1 .fwdarw. 3 N-acetylglucosamine fucosyl transferase, the resulting fucosylated derivative is cleared rapidly. Neither mannan nor derivatives of orosomucoid that are cleared by binding to receptors for galactose, N-acetylglucosamine or mannose, inhibit clearance of lactoferrin although clearance is inhibited by fucoidin. Glycoproteins containing fucose in .alpha.1 .fwdarw. 2 linkage to galactose or .alpha.1 .fwdarw. 6 linkage to N-acetylglucosamine do not inhibit lactoferrin clearance by the liver. Since clearance of other glycoproteins, such as human lactoperoxidase, also appears to be mediated through binding to the same hepatocyte receptor as lactoferrin, the fucose-specific receptor studied here may fulfill other functions than binding lactoferrin. Preliminary studies with liver homogenates and detergent extracts of liver show binding in vitro.