Belosevic M, Finbloom D S, Meltzer M S, Nacy C A
Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
J Immunol. 1990 Aug 1;145(3):831-9.
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.
在接触微生物之前用白细胞介素-2（IL-2）和γ干扰素（IFN-γ）培养的巨噬细胞，获得了抵抗专性细胞内寄生虫——硕大利什曼原虫感染的能力。在添加淋巴因子后6至8小时，这种巨噬细胞效应反应的诱导达到最大值，且与淋巴因子的处理顺序无关。巨噬细胞对感染抵抗力的激活是IL-2和IFN-γ对巨噬细胞直接作用的结果：在T细胞耗尽的驻留腹膜巨噬细胞和骨髓来源细胞（一种同质巨噬细胞群体）中均证实了这种效应反应。放射性标记的鼠重组IFN-γ、人重组IL-2以及抗IL-2受体的单克隆抗体（7D4），均以特异性和可饱和的方式与鼠骨髓来源的巨噬细胞结合，这表明未受刺激的巨噬细胞具有这两种淋巴因子的受体。用IFN-γ处理巨噬细胞可增加IL-2的特异性结合；然而，用IL-2处理细胞并未上调IFN-γ受体。在暴露于重组IL-2和重组IFN-γ期间添加蛋白质或RNA合成抑制剂（放线菌酮、依米丁、放线菌素D），完全消除了巨噬细胞表达这种效应反应的能力；蛋白激酶C、磷脂酶C或钙再分布的抑制剂则没有作用。在用IL-2和IFN-γ激活巨噬细胞后，培养液中的可溶性多克隆抗TNF-α抗体完全消除了对感染抵抗力的表达。T细胞生长激素IL-2作为IFN-γ的辅助因子，用于诱导巨噬细胞的抗菌活性，而TNF-α可能是受这两种淋巴因子调节的抗感染效应分子。
