Hepatic asialoglycoprotein receptors

E. A. L. Biessen, D. M. Beuting, H. F. Bakkeren, J. Kuiper, and T. J. C. Van Berkel, Evaluation of the particle size as a determinant of affinity for the hepatic galactose-particle and asialoglycoprotein receptor, Hepatic Endocytosis of Lipids and Proteins (E. Windier, H. Greten, eds.), W. Zuckschwerdt Verlag, Miinchen, 1992, pp. 157-165. 

The asialoglycoprotein receptor has been widely used because it is a part of the surveillance system in the circulation and it removes proteins as they age by the spontaneous loss of sialic acid (212, 213). This hepatic receptor has been widely used (214) to deliver reporter genes to the rat liver in vivo. In a study, a ligand for the asialoglycoprotein receptor (ASOR) was covalently linked to poly(L-lysine). After hepatic uptake of the complex of DNA and the ASOR-poly (L-lysine) conjugate, the reporter gene product is found in the liver (214). Other examples of receptor-mediated... 

T. Eto and H. Takahashi, Enhanced inhibition of hepatitis B virus production by asialoglycoprotein receptor-directed interferon, Nature Med. 5 577-581 (1999). 

Asialofetuin is an asialoglycoprotein containing terminal galactosyl residues that have been used to target liposomes to the liver. There was seven-fold enhancement in CAT expression in the liver when succinylatcd asialofetuin was added to preformed plasmid/ DOTAP Chol complexes to provide a ligand for hepatic asialoglycoprotein receptor. 

The canonical asialoglycoprotein receptor (ASGPR) is the hepatic lectin (HL) common to mammals, first reported in the rat in 1974 by Ashwell and co-workers [98] (reviewed in [99,100,101]. Rat HL is a complex of two homologous C-type lectins (46kDa HL-1 and... 

AAG is synthesized primarily by the hepatic parenchymal cells, but granulocytes and monocytes may also contribute to plasma levels in sepsis. Catabolism is believed to be primarily by removal of desialylated AAG by hepatic asialoglycoprotein receptors. The plasma half-life of intact AAG is 3 days, whereas that of the desialylated protein is only a few minutes. 

Carbohydrate-specific hepatic receptor-mediated clearance mechanisms include the asialoglycoprotein, S04-GalNAc and Man receptors [235,236]. The asialoglycoprotein receptor on liver hepatocytes is most significant and accounts for the short circulatory half-life of proteins lacking terminal SA [237]. Reliable quantitative analysis of SA will be an important aspect of quality control for glycoprotein pharmaceuticals. For glycoproteins produced in recombinant S. cerevisiae and insect cells which possess terminal Man or Gn moieties, the Man receptor presumably represents a major clearance mechanism [229]. 

The mammalian hepatic lectin (also referred to as the asialoglycoprotein receptor) is found on the surface of liver cells. The protein directs the clearance from the serum... 

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