Binding kinetics of monomeric and aggregated IgG to Kupffer cells and hepatocytes of mice.
The binding kinetics of human monomeric IgG and stable heat-aggregated IgG (A-IgG) to Fc receptors of hepatocytes and Kupffer cells isolated from mice was studied. After injection of radiolabelled proteins the 60-70% of hepatic uptake was recovered in parenchymal cells (hepatocytes). In experiments in vitro the A-IgG bound in larger amounts to hepatocytes and Kupffer cells than monomeric IgG. The association rate constants of aggregates were somewhat higher for Kupffer cells than for hepatocytes whereas the percentage uptake of aggregates by Kupffer cells was only 5-15% of that of hepatocytes. The equilibrium constants of aggregates binding to both cells amounted to 0.4-1 X 10(8) M-1 for A-IgG compared with an equilibrium constant for monomeric IgG of 1-2 X 10(7)M-1. The maximum number of IgG and A-IgG molecules bound per cell was higher on hepatocytes (mean 14 X 10(6)) than on Kupffer cells (mean 2 X 10(5)) which is in agreement with the higher binding capacity of hepatocytes for these proteins observed in vivo and in vitro experiments. The ability to compete for receptor binding seemed to reside exclusively in the Fc portion of IgG since F(ab')2 fragments of IgG failed to inhibit labelled monomeric IgG or A-IgG. The receptor seems to be specific for IgG since unlabelled monomeric IgA demonstrated no binding inhibition of labelled IgG or A-IgG on hepatocytes and Kupffer cells. The overall results further suggest that hepatocytes might through Fc receptors play a collaborative role with the mononuclear phagocytic system in the clearance of circulating immune complexes.
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D006358:Hot Temperature; D007074:Immunoglobulin G / Q000378:metabolism*; D007700:Kinetics; D007728:Kupffer Cells / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D011961:Receptors, Fc / Q000032:analysis / Q000276:immunology; D017452:Receptors, IgG
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D046911:Macromolecular Substances; D011961:Receptors, Fc; D017452:Receptors, IgG