title: The role of gamma interferon in the generation of human macrophages cytotoxic for Entamoeba histolytica trophozoites.
abstract: Upon exposure to Entamoeba histolytica antigen, lymphocytes from patients treated for amebic liver abscess produce lymphokines which activate monocyte-derived macrophages to kill E. histolytica trophozoites. We now demonstrate that gamma interferon (IFN-gamma) is produced by these stimulated lymphocytes and is sufficient but not exclusively necessary to activate monocyte-derived macrophage amebicidal activity. Supernatants from mononuclear cells of 7 patients when stimulated with amebic antigen contained more IFN-gamma than comparable supernatants derived from control cells (1,862 U/ml vs. 174 U/ml geometric means, P less than 0.01); IFN-gamma levels were similar in patient and control supernatants following concanavalin A stimulation. Macrophages activated solely by partially purified IFN-gamma or recombinant human IFN-gamma (300 U/ml) killed 47% of virulent amebae by 6 hr at 37 degrees C. Monocyte-derived macrophages stimulated with lymphokines elicited by amebic antigen or concanavalin A killed 48% and 57% of axenic E. histolytica trophozoites, respectively, over 6 hr at 37 degrees C (P less than 0.001 for each compared to control). Macrophages incubated with the identical lymphokines, but in the presence of monoclonal antibody to IFN-gamma, were only able to kill 18% and 27% of amebae, respectively, at 6 hr (P less than 0.05 to control or when antibody to IFN-gamma was not present). If antibody to IFN-gamma was added to the stimulating lymphokine, more macrophages died during interaction with amebae (P less than 0.05). In summary, IFN-gamma has a major but not exclusive role in activating human monocyte-derived macrophages in vitro to kill virulent E. histolytica trophozoites.
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004748:Entamoeba histolytica / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008101:Liver Abscess, Amebic / Q000276:immunology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D008222:Lymphokines; D011994:Recombinant Proteins; D003208:Concanavalin A; D007371:Interferon-gamma