METAL-CATALYZED OXIDATION OF IMMUNOGLOBULIN-G IMPAIRS FC RECEPTOR-MEDIATED BINDING TO MACROPHAGES

Enhanced oxidative stress is a feature of inflammatory and infectious conditions. proteins may be important targets of oxidation and this ma y alter their function. We evaluated whether metal-catalyzed oxidation of Iec could alter its ability to bind to Fc receptors on macrophages . Human IgG incubated with an FeCl3/EDTA/ascorbate metal-catalyzed oxi dation system resulted in a significant increase in carbonyl content, a measure of protein oxidation, compared to IgG treated with EDTA alon e (control). Western blot analysis using an antibody to oxidized prote in revealed an increase in antibody binding to both the heavy (Fc port ion-containing) and light chains of IgG treated with the oxidizing sys tem. Western blot analysis of papain-digested Ige confirmed oxidative modification of the Fc portion. Binding studies carried our with J774. 16 macrophages demonstrated significantly diminished ability of the ox idized IgG to bind to macrophage Fc receptors compared to control IgG. These data demonstrate that IgG is susceptible to metal-catalyzed oxi dation and that this impairs its ability to bind to macrophage Fc rece ptors, Oxidation of IgG might play a role in modulating immune functio n in infection and disorders associated with immune complex formation by diminishing IgG binding to phagocytic cells. (C) 1998 Elsevier Scie nce Inc.