IL-2. A cofactor for induction of activated macrophage resistance to infection

J Immunol. 1990 Aug 1;145(3):831-9.

Abstract

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.

MeSH terms

  • Animals
  • Calcimycin / pharmacology
  • Immunity, Innate / drug effects
  • Infections / immunology*
  • Interferon-gamma / pharmacology
  • Interleukin-2 / pharmacology*
  • Macrophage Activation / drug effects
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Receptors, Interleukin-2 / analysis
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Interleukin-2
  • Receptors, Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Calcimycin
  • Interferon-gamma
  • Tetradecanoylphorbol Acetate