IL-2. A cofactor for induction of activated macrophage resistance to infection.
Macrophages cultured with IL-2 and IFN-gamma before exposure to microorganisms developed the ability to resist infection with the obligate intracellular parasite, Leishmania major. The induction of this macrophage effector response was maximal by 6 to 8 h after lymphokine addition, and was independent of lymphokine treatment sequence. Activation of macrophages for resistance to infection was the result of the direct action of IL-2 and IFN-gamma on macrophages: the effector reaction was demonstrated in both resident peritoneal macrophages depleted of T cells and bone marrow-derived cells, a homogeneous macrophage population. Radiolabeled murine rIFN-gamma, human rIL-2, and mAb to the IL-2R (7D4), each bound to murine bone marrow-derived macrophages in a specific and saturable manner, which suggested that unstimulated macrophages have receptors for both lymphokines. Treatment of macrophages with IFN-gamma increased the specific binding of IL-2; treatment of cells with IL-2, however, did not up-regulate the IFN-gamma-R. Addition of protein or RNA synthesis inhibitors (cycloheximide, emetine, actinomycin D) during exposure to rIL-2 and rIFN-gamma totally abrogated the ability of macrophages to express this effector reaction; inhibitors of protein kinase C, PG, or calcium redistribution had no effect. Soluble polyclonal anti-TNF-alpha antibodies in culture fluids after activation of macrophages with IL-2 and IFN-gamma totally abrogated the expression of resistance to infection. The T cell growth hormone IL-2 acts as cofactor with IFN-gamma for induction of a macrophage antimicrobial activity, and TNF-alpha may be the effector molecule for resistance to infection regulated by these two lymphokines.
Belosevic
M
M
Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Finbloom
D S
DS
Meltzer
M S
MS
Nacy
C A
CA
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D007113:Immunity, Innate / Q000187:drug effects; D007239:Infections / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D000001:Calcimycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate