Andersson Anders, Malmhäll Carina, Houltz Birgitta, Tengvall Sara, Sjöstrand Margareta, Qvarfordt Ingemar, Lindén Anders, Bossios Apostolos
Respiratory Medicine and Allergology, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Krefting Research Center, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Int J Chron Obstruct Pulmon Dis. 2016 Sep 15;11:2245-2258. doi: 10.2147/COPD.S103758. eCollection 2016.
BACKGROUND: Long-term exposure to tobacco smoke causes local inflammation in the airways that involves not only innate immune cells, including NK cells, but also adaptive immune cells such as cytotoxic (CD8) and helper (CD4) T-cells. We have previously demonstrated that long-term tobacco smoking increases extracellular concentration of the CD4-recruiting cytokine interleukin (IL)-16 locally in the airways. Here, we hypothesized that tobacco smoking alters IL-16 biology at the systemic level and that this effect involves oxygen free radicals (OFR). METHODS: We quantified extracellular IL-16 protein (ELISA) and intracellular IL-16 in NK cells, T-cells, B-cells, and monocytes (flow cytometry) in blood samples from long-term tobacco smokers with and without chronic obstructive pulmonary disease (COPD) and in never-smokers. NK cells from healthy blood donors were stimulated with water-soluble tobacco smoke components (cigarette smoke extract) with or without an OFR scavenger (glutathione) in vitro and followed by quantification of IL-16 protein. RESULTS: The extracellular concentrations of IL-16 protein in blood did not display any substantial differences between groups. Notably, intracellular IL-16 protein was detected in all types of blood leukocytes. All long-term smokers displayed a decrease in this IL-16 among NK cells, irrespective of COPD status. Further, both NK and CD4 T-cell concentrations displayed a negative correlation with pack-years. Moreover, cigarette smoke extract caused release of IL-16 protein from NK cells in vitro, and this was not affected by glutathione, in contrast to the decrease in intracellular IL-16, which was prevented by this drug. CONCLUSION: Long-term exposure to tobacco smoke does not markedly alter extracellular concentrations of IL-16 protein in blood. However, it does decrease the intracellular IL-16 concentrations in blood NK cells, the latter effect involving OFR. Thus, long-term tobacco smoking exerts an impact at the systemic level that involves NK cells; innate immune cells that are critical for host defense against viruses and tumors - conditions that are overrepresented among smokers.
背景：长期接触烟草烟雾会导致气道局部炎症，这不仅涉及天然免疫细胞，包括自然杀伤（NK）细胞，还涉及适应性免疫细胞，如细胞毒性（CD8）和辅助性（CD4）T细胞。我们之前已经证明，长期吸烟会使气道局部募集CD4的细胞因子白细胞介素（IL）-16的细胞外浓度增加。在此，我们假设吸烟会在系统水平上改变IL-16的生物学特性，并且这种效应涉及氧自由基（OFR）。 方法：我们对患有和未患有慢性阻塞性肺疾病（COPD）的长期吸烟者以及从不吸烟者的血液样本中的细胞外IL-16蛋白（酶联免疫吸附测定）和NK细胞、T细胞、B细胞及单核细胞中的细胞内IL-16（流式细胞术）进行了定量分析。来自健康献血者的NK细胞在体外被水溶性烟草烟雾成分（香烟烟雾提取物）刺激，添加或不添加OFR清除剂（谷胱甘肽），随后对IL-16蛋白进行定量分析。 结果：各组血液中IL-16蛋白的细胞外浓度没有显示出任何实质性差异。值得注意的是，在所有类型的血液白细胞中都检测到了细胞内IL-16蛋白。所有长期吸烟者的NK细胞中这种IL-16均减少，与COPD状态无关。此外，NK细胞和CD4 T细胞的浓度均与吸烟包年数呈负相关。此外，香烟烟雾提取物在体外导致NK细胞释放IL-16蛋白，与细胞内IL-16的减少不同，这不受谷胱甘肽的影响，而谷胱甘肽可防止细胞内IL-16的减少。 结论：长期接触烟草烟雾不会显著改变血液中IL-16蛋白的细胞外浓度。然而，它确实会降低血液NK细胞中的细胞内IL-16浓度，后一种效应涉及OFR。因此，长期吸烟在系统水平上产生影响，涉及NK细胞；NK细胞是对宿主抵御病毒和肿瘤至关重要的天然免疫细胞，而这些情况在吸烟者中更为常见。
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