Induction, maintenance, and reinduction of tumoricidal activity in bone marrow-derived mononuclear phagocytes by Corynebacterium parvum. Evidence for the involvement of a T cell- and interferon-gamma-independent pathway of macrophage activation.
Rat bone marrow-derived mononuclear phagocytes, virtually homogeneous with respect to the cell lineage, do not exhibit spontaneous tumoricidal activity in the resting state. When incubated with macrophage-activating lymphokines, rat recombinant interferon-gamma (IFN), or heat-killed Corynebacterium parvum, bone marrow-derived mononuclear phagocytes readily evolve tumoricidal activity. Whereas tumoricidal activity induced by lymphokines and/or rat recombinant IFN-gamma is short-lived, that elicited by C. parvum is maintained for at least 2 wk, provided that the C. parvum organisms are continuously present in the culture. After washing off extracellular organisms, C. parvum-induced tumoricidal activity decays rapidly, suggesting that sustained extracellular stimulation is required for its maintenance. Induction of tumoricidal activity by macrophage-activating lymphokines and/or rat recombinant IFN-gamma is fully prevented by polyclonal and monoclonal anti-IFN-gamma antibodies; in contrast, induction by C. parvum is not affected by anti-IFN-gamma. Since induction of tumoricidal activity by C. parvum takes place irrespective of the presence of anti-Thy-1 antisera or cyclosporin A, T cells and/or their products appear not to be involved in this type of macrophage activation. Accordingly, present findings provide evidence for the existence of lymphokine-independent pathways of macrophage activation.
D000818:Animals; D001854:Bone Marrow Cells; D003602:Cytotoxicity, Immunologic; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D009374:Neoplasms, Experimental / Q000276:immunology*; D010586:Phagocytes / Q000276:immunology*; D011070:Poly I-C / Q000494:pharmacology; D011425:Propionibacterium acnes / Q000276:immunology*; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D007371:Interferon-gamma; D011070:Poly I-C