INTERLEUKIN-12-STIMULATED NATURAL-KILLER-CELLS CAN ACTIVATE HUMAN MACROPHAGES TO INHIBIT GROWTH OF MYCOBACTERIUM-AVIUM
INTERLEUKIN-12-STIMULATED NATURAL-KILLER-CELLS CAN ACTIVATE HUMAN MACROPHAGES TO INHIBIT GROWTH OF MYCOBACTERIUM-AVIUM
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DOI：
10.1128/iai.63.10.4099-4104.1995
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发表时间：
1995-10-01
影响因子：
3.1
通讯作者：
YOUNG, LS
中科院分区：
文献类型：
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作者：
BERMUDEZ, LE;WU, M;YOUNG, LS
白细胞介素-12（IL-12）是影响NK细胞和T细胞的许多生物学功能的关键细胞因子。我们之前已经证明，人和小鼠NK细胞在宿主防御鸟分支杆菌复合体方面都很重要，并且通过分泌细胞因子诱导巨噬细胞抑制细胞内M的生长来发挥作用。avium探讨IL-12在M.禽支原体复合体感染后，我们用0.01 - 1 ng/ml的重组人IL-12刺激人NK细胞24小时，并用组织培养上清液处理感染M. avium IL-12对M.病毒感染的巨噬细胞，但IL-12处理的NK细胞培养上清液激活巨噬细胞，抑制细胞内M.以剂量依赖的方式。用IL-12与肿瘤坏死因子α（TNF-α）或IL-1联合刺激NK细胞，增加了NK细胞培养物上清液限制M.与IL-12处理的NK细胞的培养上清液相比，巨噬细胞内的禽流感病毒生长。来自未刺激的NK细胞的上清液的结果与来自未处理的对照的上清液的结果相似。用抗TNF-α、抗粒细胞-巨噬细胞集落刺激因子而非抗γ干扰素抗体处理IL-12刺激的NK细胞上清液，可降低NK细胞上清液诱导抗M。感染的巨噬细胞中的抗体活性。在加入IL-12刺激的NK细胞上清液之前，用抗转化生长因子β抗体处理巨噬细胞单层，与IL-12处理的NK细胞上清液相比，抗鸟支原体活性增加。这些结果表明IL-12在宿主防御M中发挥作用。IL-12的作用主要依赖于TNF-α和粒细胞-巨噬细胞集落刺激因子。
Interleukin-12 (IL-12) is a critical cytokine that affects many of the biological functions of NK cells and T cells. We have previously shown that both human and murine NK cells are important in host defense against Mycobacterium avium complex and act by secreting cytokines that induce macrophages to inhibit the growth of intracellular M. avium. To define the role of IL-12 in M. avium complex infection, we stimulated human NK cells with recombinant human IL-12 at 0.01 to 1 ng/ml for 24 h and used the tissue culture supernatant td treat human monocyte-derived macrophage monolayers infected with M. avium. IL-12 had no direct effect on M. avium-infected macrophages, but culture supernatant from IL-12-treated NK cells activated macrophages to inhibit the growth of intracellular M. avium in a dose-dependent manner. Stimulation of NK cells with IL-12 in combination with tumor necrosis factor alpha (TNF-alpha) or IL-1 increased the ability of supernatant from NK-cell culture to limit M. avium growth within macrophages, compared,vith that of culture supernatant from IL-12-treated NK cells. Results with supernatant from nonstimulated NK cells were similar to those with supernatant from untreated controls. Treatment of supernatant from IL-12-stimulated NK cells with anti-TNF-alpha, anti-granulocyte-macrophage colony-stimulating factor, but not anti-gamma interferon antibodies decreased the ability of NK-cell supernatant to induce anti-M. avium activity in infected macrophages. Treatment of macrophage monolayers with anti-transforming growth factor beta antibody before adding supernatant from IL-12-stimulated NK cells was associated with an increase of anti-M, avium activity compared with that of supernatant from IL-12-treated NK cells. These results suggest that IL-12 has a role in host defense against M. avium and that the effect of IL-12 is dependent chiefly on TNF-alpha and granulocyte-macrophage colony-stimulating factor.