Murine macrophages secrete interferon gamma upon combined stimulation with interleukin (IL)-12 and IL-18: A novel pathway of autocrine macrophage activation.
Interferon (IFN)-gamma, a key immunoregulatory cytokine, has been thought to be produced solely by activated T cells and natural killer cells. In this study, we show that murine bone marrow- derived macrophages (BMMPhi) secrete large amounts of IFN-gamma upon appropriate stimulation. Although interleukin (IL)-12 and IL-18 alone induce low levels of IFN-gamma mRNA transcripts, the combined stimulation of BMMPhi with both cytokines leads to the efficient production of IFN-gamma protein. The macrophage-derived IFN-gamma is biologically active as shown by induction of inducible nitric oxide synthase as well as upregulation of CD40 in macrophages. Our findings uncover a novel pathway of autocrine macrophage activation by demonstrating that the macrophage is not only a key cell type responding to IFN-gamma but also a potent IFN-gamma-producing cell.
Munder
M
M
Max-Planck-Institut für Immunbiologie, D-79108 Freiburg, Germany.
Mallo
M
M
Eichmann
K
K
Modolell
M
M
D000818:Animals; D019898:Autocrine Communication; D001854:Bone Marrow Cells / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D004357:Drug Synergism; D005246:Feedback; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D018664:Interleukin-12 / Q000494:pharmacology*; D020382:Interleukin-18; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis
D016207:Cytokines; D020382:Interleukin-18; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma