IFN-gamma-induced production of monocyte cytotoxic factor.
The effect of activating human monocytes in vitro with recombinant Interferon-gamma (IFN-gamma) and lymphokines on monocyte-mediated cytotoxicity and on the production of cytotoxic protein factor(s) (CF), has been investigated. Lymphokines and IFN-gamma enhanced both cytotoxicity and CF production in a dose-dependent manner. A monoclonal antibody against human IFN-gamma abrogated the lymphokine-induced cytotoxic activity and CF production completely, indicating that the actual monocyte-activating factor in the lymphokine supernatant was IFN-gamma. At concentrations of 10(3)-10(4) U/ml, IFN-gamma induced an enhanced release of CF from the monocytes. However, IFN-gamma at concentrations (less than 100 U/ml) present in our lymphokine preparation was not sufficient to induce enhanced CF release. Since IFN-gamma at concentrations less than 100 U/ml activated monocytes for cytotoxicity, CF as an extracellular factor in the supernatant does not appear to be essential for monocyte-mediated cytotoxicity. However, using neutralizing antiserum raised against purified CF, indirect immunofluorescence microscopy revealed that IFN-gamma induced a marked accumulation of CF on the monocyte membrane. Taken together, the data shows that IFN-gamma is both necessary and sufficient at concentrations less than 100 U/ml for inducing monocyte-mediated cytotoxicity and production of CF as a membrane-associated component, but not as a released factor, suggesting that CF may function as a membrane-associated cytotoxin in monocyte-mediated cytotoxicity.
D000911:Antibodies, Monoclonal / Q000502:physiology; D001667:Binding, Competitive; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D003603:Cytotoxins / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D008222:Lymphokines / Q000494:pharmacology; D008262:Macrophage Activation; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D003603:Cytotoxins; D007106:Immune Sera; D008222:Lymphokines; D007371:Interferon-gamma