Immune complexes increase nitric oxide production by interferon-γ-stimulated murine macrophage-like JT74.16 cells

Murine macrophage-like 5774.16 cells were tested for changes in nitric oxide production upon incubation with immune complexes. Cryptococcus neoformans capsular polysaccharide and polysaccharide-specific monoclonal antibodies were added to J774.16 cells in the presence and absence of recombinant murine interferon-γ (IFN-γ). The effect of immune complexes on nitrite synthesis was both concentration dependent and isotype dependent. In the presence of IFN-γ, immune complexes of IgG1, IgG2a, IgG2b, or IgG3 isotype increased nitrite levels, whereas complexes of IgM isotype did not. Immune complexes did not alter nitrite production by unstimulated macrophage. Antibody alone, antigen alone, and antigen with irrelevant IgG1 antibody did not augment nitrite formation, either in the presence or absence of IFN-γ, indicating a requirement for FcγR cross-linking. These results suggest that IgG isotypes may offer additional protect-ion against pathogens by enhancing macrophage nitric pride production.