Priming and triggering of tumoricidal and schistosomulicidal macrophages by two sequential lymphokine signals: interferon-gamma and macrophage cytotoxicity inducing factor 2.
We describe a new lymphokine activity, macrophage cytotoxicity inducing factor 2 (MCIF2), in the T cell mitogen-induced supernatant of a murine T cell clone in long-term culture. MCIF2 has the following properties: it elutes from a Sephadex G-100 column in three m.w. forms (10, 34, and 100 KD); it is acid labile (pH 2 to 4) and heat sensitive (80 min at 56 degrees C); it is not constitutively secreted, coexists in the same supernatant with immune interferon (IFN-gamma), and synergizes with IFN-gamma for induction of tumoricidal and schistosomulicidal resident peritoneal mouse macrophages. We uncoupled this synergy and show that IFN-gamma serves as the first ("priming") and MCIF2 as the second ("triggering") signal for macrophage activation. Application of the lymphokines in the reverse order was ineffective. These data demonstrate a two-step mechanism of macrophage activation.
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002999:Clone Cells / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004357:Drug Synergism; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology*; D008222:Lymphokines / Q000032:analysis / Q000502:physiology*; D008262:Macrophage Activation; D016215:Macrophage-Activating Factors; D008297:Male; D012515:Mast-Cell Sarcoma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011994:Recombinant Proteins; D012555:Schistosomiasis mansoni; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
D008222:Lymphokines; D016215:Macrophage-Activating Factors; D011994:Recombinant Proteins; D007371:Interferon-gamma