Enhanced alternative complement pathway-dependent degradation of soluble immunoglobulin aggregates by macrophages

The role of complement in the processing of soluble immune aggregates by guinea-pig peritoneal macrophages was studied in a homologous system in vitro. Stable soluble aggregates of guinea-pig IgG1 are shown to activate the alternative pathway in C4-deficient guinea-pig serum. At 37 degrees and under serum-free conditions, adherent peritoneal macrophages degraded in 2 hr at least 50% of the available immunoglobulin aggregates. Addition of fresh C4D serum to the incubation mixtures caused a two-fold increase in the rate of degradation. The stimulating effect of C4D serum was complement-mediated, because it was abolished by heat treatment, CoVF treatment and specific C3 depletion of the C4D serum. Functional inactivation of C3 receptors on the macrophages by trypsin also impeded the stimulating effect of fresh C4D serum. The results indicate that the alternative pathway of complement contributes significantly to the elimination of soluble immune complexes by mononuclear phagocytes.