Histidine-rich glycoprotein regulates the binding of monomeric IgG and immune complexes to monocytes

Histidine-rich glycoprotein (HRG) is a relatively abundant plasma protein w hich we have shown previously inhibits the formation of insoluble immune co mplexes (IC). In this study we examined the ability of HRG to regulate the binding of monomeric IgG and IC to monocytes. Initial studies demonstrated that HRG interacts with Fc gamma RI on the monocytic cell line THP1 and blo cks the binding of monomeric IgG to these cells, However, despite totally b locking the binding of monomeric IgG to Fc gamma RI, pre-incubation of THP1 cells with HRG had no effect on the binding of IC to these cells. in contr ast, depending on the HRG:IgG molar ratio, pre-incubation of monomeric IgG with HRG resulted in either enhanced or reduced IgG binding to Fc gamma RI. Similarly, under certain highly defined conditions, incorporation of HRG i n IgG-containing IC potentiated the binding of IC to THP1 cells. The key co nditions involved incorporating approximately equimolar concentrations of H RG and IgG in the IC, the IC being formed at a near equivalence antigen:ant ibody ratio and usually physiological concentration (20 mu M) Of Zn2+ being present. Collectively these observations indicate that HRG is an important regulator of IC uptake by monocytes. Thus HRG can interact with Fc gamma R I on monocytes and block monomeric IgG binding, whereas when incorporated i n IgG containing IC, HRG can enhance the uptake of IC by monocytes, probabl y via its heparan sulfate binding domain.