Regulation of Fc receptors for IgG on cultured rat mesangial cells. Localization of immune complexes (IC) to the mesangium may contribute to glomerular disease. Recently, we and others characterized Fc receptors (FcγR) for IgG-IC on mesangial cells (MC). This study examines regulation of FcγR by cAMP, interferon γ (IFN-γ) and by macrophage colony stimulating factor (CSF-1), an agent controlling FcγR in leukocytes and generated by MC. Preincubation of MC (3rd to 6th subculture) with CSF-1, db-cAMP or IFN-γ for two to 48 hours resulted in a time dependent (maximal 24 to 48 hrs) two- to threefold increase of specific [¹²⁵I] IgG-IC binding to MC at 4°C. The increase of Fc receptors induced by CSF-1, db-cAMP or IFN-γ was confirmed by enhanced binding of the monoclonal anti-Fc receptor antibody 2.4G2 to MC. Uptake of IgG-IC at 37°C was also enhanced in MC pretreated with CSF-1, db-cAMP or IFN-γ. This indicates that the increase in binding for IgG-IC is associated with functional receptors Immunopre-cipitation of extracts of [¹²⁵I] surface labeled MC with polyclonal anti-FcγR-Ab followed by SDS-PAGE also showed increased amounts of [¹²⁵I] FcγR protein after pretreatment with CSF-1, db-cAMP or IFN-γ. The pretreatment also enhanced staining of MC with anti-FcγR-Ab by immunogold-silver enhancement technique. We conclude that MC express FcγR for IgG-IC that can be regulated by CSF-1, cAMP and IFN-γ, factors that may be important in glomerular immune injury.