The role of sialic acid in the functional activity and the hepatic clearance of C1-INH.
The immunochemical properties, catabolic clearance, and organ distribution of highly purified radiolabeled human C1-INH were studied after treatment with glycosidases. The antigenicity and C1s inhibitory activity of C1-INH were unimpaired after removal of sialic acid residues (60%) or sialic acid and galactose residues (60 and 20%, respectively) with immobilized neuraminidase and beta-galactosidase. Treatment of C1-INH with neuraminidase was associated with increased cathodal migration of the glycoprotein. In vivo studies in the rabbit, however, showed that removal of sialic acid residues resulted in rapid blood clearance of C1-INH and enhanced localization of the asialo C1-INH in the liver. Subsequent removal of penultimate galactose residues returned the survival time in the circulation and organ distribution to near normal. Additionally, simultaneous infusion of asialo-C1-INH with asialo alpha 1-acid glycoprotein, a protein known to bind to hepatic asialoglycoprotein receptors, dramatically extended the intravascular survival time of asialo C1-INH. In agreement with the observations on other plasma glycoproteins, these results indicate that desialylation of C1-INH results in rapid clearance by hepatic asialoglycoprotein receptors.
D000818:Animals; D002417:Cattle; D003174:Complement C1 Inactivator Proteins / Q000276:immunology / Q000378:metabolism*; D006023:Glycoproteins / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D009439:Neuraminidase / Q000494:pharmacology; D011817:Rabbits; D012794:Sialic Acids / Q000378:metabolism*
D003174:Complement C1 Inactivator Proteins; D006023:Glycoproteins; D012794:Sialic Acids; D009439:Neuraminidase