Interferon gamma-treated human macrophages display enhanced cytolysis and generation of reactive oxygen metabolites but reduced ingestion upon Fc receptor triggering.

Journal: Human Immunology
Published:
Abstract

Human monocyte-derived macrophages treated with recombinant IFN-gamma (rIFN-gamma) and control cells were assessed for three distinct effector functions, all mediated by Fc receptors. rIFN-gamma-primed macrophage displayed markedly reduced phagocytosis of IgG antibody-coated erythrocytes. In contrast, antibody-dependent cytotoxicity towards IgG-antibody-coated erythrocytes and IgG-antibody-coated erythrocyte-induced generation of reactive oxygen metabolite production were increased. The decreased phagocytosis was observed microscopically, as well as in a spectrometric and a radiometric phagocytosis assay. Evidence is presented that the observed impairment in phagocytosis is not the result of increased extracellular lysis or intracellular catabolism of IgG-antibody-coated erythrocytes and that it is not observed with particles ingested in an Fc receptor-independent manner. Enhanced production of reactive oxygen metabolites was detected most clearly by measurement of luminol-dependent chemiluminescence. Antibody-dependent cellular cytotoxicity was shown to proceed also under conditions impeding phagocytosis, and rIFN-gamma-treated macrophage exerted enhanced antibody-dependent cellular cytotoxicity under these conditions too. In all three assays, functional alterations were optimally expressed after a treatment with 500 U/ml for 46 hr. Analysis at the single-cell level revealed that the IFN-gamma-induced alterations were expressed by all macrophages and not the property of distinct macrophage subpopulations. This and earlier studies suggest that the modulation of Fc receptor-mediated macrophage effector functions by IFN-gamma is in part a post-receptor-binding event.

Authors
T Jungi, S Rüegg, A Morell