Clinic for Immunology and Rheumatology, Hannover Medical School, Hannover, Germany.
Blood. 2010 Aug 26;116(8):1308-16. doi: 10.1182/blood-2010-01-264903. Epub 2010 May 25.
Natural killer (NK) cells and polymorphonuclear cells (PMNs) play a critical role in the first line of defense against microorganisms. Upon host infection, PMNs phagocytose invading pathogens with subsequent killing by oxidative or nonoxidative mechanisms. NK cells are known to have immunoregulatory effects on T cells, B cells, dendritic cells (DCs), and monocytes through secretion of various soluble products and cell-cell contact. However, their impact on PMN survival and function is not well known. We found that soluble factors derived from cytokine-activated NK cells delay PMN apoptosis and preserve their ability to perform phagocytosis and produce reactive oxygen species (ROS). The expression patterns of CD11b and CD62L on PMNs differed according to the cytokine combination used for NK-cell stimulation. Irrespective of the NK-cell treatment, however, PMN survival was prolonged with sustained functional capacity. We found that interferon gamma, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha produced by NK cells upon stimulation with cytokines played a crucial role in NK cell-mediated effects on PMNs. Our study demonstrates that soluble factors derived from cytokine-activated NK cells send survival signals to PMNs, which would promote their accumulation and function at the site of inflammation in vivo.
自然杀伤 (NK) 细胞和多形核粒细胞 (PMN) 在抵御微生物的第一道防线中发挥着关键作用。在宿主感染时，PMN 通过吞噬入侵的病原体，随后通过氧化或非氧化机制进行杀伤。NK 细胞通过分泌各种可溶性产物和细胞-细胞接触，已知对 T 细胞、B 细胞、树突状细胞 (DC) 和单核细胞具有免疫调节作用。然而，它们对 PMN 存活和功能的影响尚不清楚。我们发现，细胞因子激活的 NK 细胞衍生的可溶性因子可延迟 PMN 凋亡，并保持其吞噬和产生活性氧物质 (ROS) 的能力。PMN 上 CD11b 和 CD62L 的表达模式根据用于刺激 NK 细胞的细胞因子组合而不同。然而，无论 NK 细胞的治疗如何，PMN 的存活时间都延长了，并且保持了持续的功能能力。我们发现，细胞因子刺激 NK 细胞产生的干扰素 γ、粒细胞-巨噬细胞集落刺激因子和肿瘤坏死因子 α 在 NK 细胞对 PMN 的介导作用中起着至关重要的作用。我们的研究表明，细胞因子激活的 NK 细胞衍生的可溶性因子向 PMN 发出存活信号，这将促进它们在体内炎症部位的积累和功能。
