CARBOHYDRATE-MEDIATED CLEARANCE OF IMMUNE-COMPLEXES FROM THE CIRCULATION - A ROLE FOR GALACTOSE RESIDUES IN THE HEPATIC-UPTAKE OF IGG-ANTIGEN COMPLEXES

Abstract

The hypothesis that galactose residues on Ig[immunoglobulin]G mediate the clearance of IgG.cntdot.antigen complexes from the circulation was evaluated. After 28 days of immunization of rats with bovine serum albumin (BSA), .apprx. 90% of anti-BSA antibody was IgG; the circulating half-life of trace amounts of BSA antigen in immunized rats was 6 min, compared to 24 h in nonimmunized rats. Soluble IgG.cntdot.125I-BSA complexes formed in vitro, under conditions of antibody excess, had a circulating half-life of 4 min in normal rats. For antigen in immunized rats or IgG.cntdot.125I-BSA complexes in normal animals, clearance was markedly inhibited by pre- or co-injection of asialofetuin, but was insensitive to large doses of fetuin, ovalbumin or mannan. Liver parenchymal cells were the major site of uptake of complexes formed in vivo or in vitro. In vitro binding of IgG.cntdot.125I-BSA complexes by isolated hepatocytes was effectively competed by asialofetuin, asialo-orosomucoid, galactose and N-acetylgalactosamine, but was unaffected by fetuin, orosomucoid, ovalbumin, mannan or mannose. Antigen-induced conformational changes in IgG probably result in recognition of galactose residues on IgG and clearance of IgG-immune complexes from the circulation by the galactose-specific receptor in hepatic parenchymal cells.