Interleukin 7 induces cytokine secretion and tumoricidal activity by human peripheral blood monocytes.
Interleukin 7 induces cytokine secretion and tumoricidal activity by human peripheral blood monocytes.
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DOI：
10.1084/jem.173.4.923
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发表时间：
1991-04-01
影响因子：
15.3
通讯作者：
Grabstein, K H
中科院分区：
文献类型：
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作者：
Alderson, M R;Tough, T W;Ziegler, S F;Grabstein, K H
外周血单核细胞可被刺激物如细菌脂多糖（LPS）诱导以分泌一系列细胞因子。我们研究了白细胞介素7（IL-7）对人外周血单个核细胞（PBMC）的作用，发现IL-7是一种较强的IL-6分泌诱导剂。用B 9杂交瘤生长因子法和酶联免疫吸附法测定IL-6蛋白水平，用北方杂交法测定IL-6 mRNA水平。详细检查显示，在PBMC中，单核细胞而不是淋巴细胞分泌IL-6以响应IL-7。与刺激T细胞生长和分化所需的低浓度IL-7（低至0.1ng/ml）相反，诱导单核细胞分泌IL-6需要相对高浓度的IL-7（至少10 ng/ml）。最佳浓度的IL-7（100 ng/ml）诱导单核细胞分泌比最佳浓度的IL-1 β（10 ng/ml）多10倍的IL-6，并且几乎与LPS一样多。然而，诱导可检测水平的IL- 6需要比IL-1 β显著更多的IL-7。单核细胞分泌IL-6的动力学与IL-7、IL-1 β或LPS的反应相同，早在培养开始后2 h，培养上清液中就可检测到IL-6蛋白。IL-4可明显抑制IL-7或LPS诱导IL-6 mRNA和IL-6分泌的能力。除了促进IL-6的产生外，IL-7还诱导单核细胞分泌免疫反应性IL-1 α、IL-1 β和肿瘤坏死因子α（TNF-α）。IL-7还诱导单核细胞/巨噬细胞对人黑色素瘤细胞靶标的杀肿瘤活性，该活性可能与IL-1 α、IL-1 β和TNF-α的分泌有关。最后，我们使用全血培养系统作为体内分析的桥梁，以证明IL-7在不存在培养基、胎牛血清和粘附塑料的情况下诱导细胞因子分泌。我们的数据表明，IL-7，除了调节淋巴细胞的生长和分化，对单核细胞谱系的细胞具有强大的影响。因此，IL-7可能是炎症和巨噬细胞对肿瘤的免疫应答中的重要介质。
Peripheral blood monocytes can be induced by stimuli such as bacterial lipopolysaccharide (LPS) to secrete an array of cytokines. We have studied the effects of interleukin 7 (IL-7) on human peripheral blood mononuclear cells (PBMC) and found that IL-7 is a relatively potent inducer of IL-6 secretion IL-6 protein levels were determined either by the B9 hybridoma growth factor assay or by enzyme-linked immunosorbent assay, and mRNA for IL-6 was analyzed by Northern hybridization. Detailed examination revealed that, among PBMC, monocytes, rather than lymphocytes, were secreting IL-6 in response to IL-7. In contrast to the low concentrations of IL-7 required to stimulate T cell growth and differentiation (as low as 0.1 ng/ml), relatively high concentrations of IL-7 were necessary to induce IL-6 secretion by monocytes (at least 10 ng/ml). An optimal concentration of IL-7 (100 ng/ml) induced monocytes to secrete 10-fold more IL-6 than an optimal concentration of IL-1 beta (10 ng/ml), and almost as much as LPS. However, significantly more IL-7 than IL-1 beta was required to induce detectable levels of IL- 6. The kinetics of IL-6 secretion by monocytes were identical in response to IL-7, IL-1 beta, or LPS, with IL-6 protein detectable in culture supernatants as early as 2 h after the initiation of culture. IL-4 was found to markedly inhibit the ability of IL-7 or LPS to induce IL-6 mRNA and IL-6 secretion. In addition to promoting IL-6 production, IL-7 induced the secretion of immunoreactive IL-1 alpha, IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) by monocytes. IL-7 also induced monocyte/macrophage tumoricidal activity against a human melanoma cell target, an activity that may be related to the secretion of IL-1 alpha, IL-1 beta, and TNF-alpha. Finally, we used a whole blood culture system as a bridge to in vivo analysis to demonstrate that IL-7 induces cytokine secretion in the absence of culture medium, fetal calf serum, and adherence to plastic. Our data suggest that IL-7, in addition to regulating lymphocyte growth and differentiation, has potent effects on cells of the monocytic lineage. Thus, IL-7 may be an important mediator in inflammation and in the macrophage immune response to tumors.