Interferon-gamma is required in activation of macrophages for tumor cytotoxicity.
The participation of interferon-gamma in activation of murine macrophages for tumor cell lysis was investigated. Biochemically macrophage activation factor and interferon-gamma have not been separated. Antiviral titers correlated closely with macrophage activation in antigen- or mitogen-induced spleen cell supernatants. A monoclonal rat antibody that neutralized virus-induced interferon was also found to neutralize interferon-gamma in such supernatants. These monoclonal antibodies were coupled to CH-Sepharose 4B and used for absorption of antiviral activity from mitogen-induced spleen cell supernatants. Absorption of the interferon was paralleled by the reduction of the macrophage-activating capacity of the supernatants. Data from control absorptions supported the specificity of the absorption effect. These results indicate that interferon-gamma is required for activation of macrophages for tumor cell lysis. These results can be interpreted in two ways: (a) the monoclonal antibodies cross-react with interferon-gamma and with a mediator that is required for activation of macrophages for tumor cell lysis or (b) interferon-gamma itself is an essential cofactor for macrophage activation.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology*; D007163:Immunosorbent Techniques; D007371:Interferon-gamma / Q000032:analysis / Q000502:physiology*; D007376:Interleukin-2 / Q000032:analysis; D008222:Lymphokines / Q000502:physiology; D008262:Macrophage Activation; D016215:Macrophage-Activating Factors; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009500:Neutralization Tests; D051381:Rats; D011919:Rats, Inbred Strains; D014721:Vesicular stomatitis Indiana virus / Q000254:growth & development
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D008222:Lymphokines; D016215:Macrophage-Activating Factors; D007371:Interferon-gamma