Brandsma Corry-Anke, Hylkema Machteld N, Luinge Marjan A, Geerlings Marie, Klok Pieter A, Cassee Flemming R, Timens Wim, Postma Dirkje S, Kerstjens Huib A M
Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Inhal Toxicol. 2008 Jan;20(2):183-9. doi: 10.1080/08958370701821342.
Cigarette smoke is the most important cause for the development of chronic obstructive pulmonary disease (COPD). Since only a minority of smokers and some nonsmokers develop COPD, other factors must be involved as well. NO2 is an important air pollutant associated with respiratory symptoms in humans and emphysema development in animal models. We hypothesized that combined exposure to NO2 and cigarette smoke will enhance pulmonary inflammation and emphysema development. Mice were exposed to 20 ppm NO2 for 17 h/day, to 24 puffs of cigarette smoke 2 times per day, to their combination, or to control air for 5 days/wk during 4 wk. Following the last NO2 exposure and within 24 h after the last smoke exposure the mice were sacrificed. Lungs were removed and analyzed for several inflammatory parameters and emphysema. Cigarette smoke exposure increased eosinophil numbers and levels of tumor necrosis factor (TNF)-alpha, KC, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6. NO2 exposure increased goblet cells, eosinophils, and the levels of IL-6, while it decreased the levels of IL-10. Four weeks of NO2, cigarette smoke, or their combination was not sufficient to induce significant emphysema, nor did it lead to increased numbers of lymphocytes, neutrophils, or macrophages in lung tissue. Instead, NO2 exposure attenuated the smoke-induced increases in levels of TNF-alpha, KC, and MCP-1. These dampening effects of NO2 may be due to modulating effects of NO2 on cytokine production by macrophages and epithelial cells, which have been reported earlier. The next step is to translate these findings of combined, controlled exposure in animals to the human situation.
香烟烟雾是慢性阻塞性肺疾病（COPD）发展的最重要原因。由于只有少数吸烟者和一些非吸烟者会患上COPD，因此必然还涉及其他因素。二氧化氮（NO₂）是一种重要的空气污染物，与人类的呼吸道症状以及动物模型中的肺气肿发展有关。我们假设，同时暴露于NO₂和香烟烟雾会加剧肺部炎症和肺气肿的发展。将小鼠每周5天、持续4周暴露于20 ppm的NO₂中，每天暴露17小时；或每天2次、每次暴露于24口香烟烟雾中；或同时暴露于两者；或暴露于对照空气中。在最后一次NO₂暴露后以及最后一次烟雾暴露后24小时内，处死小鼠。取出肺部并分析多种炎症参数和肺气肿情况。暴露于香烟烟雾会增加嗜酸性粒细胞数量以及肿瘤坏死因子（TNF）-α、KC、单核细胞趋化蛋白（MCP）-1和白细胞介素（IL）-6的水平。暴露于NO₂会增加杯状细胞、嗜酸性粒细胞以及IL-6的水平，同时会降低IL-10的水平。四周的NO₂、香烟烟雾或两者联合暴露不足以诱发显著的肺气肿，也未导致肺组织中淋巴细胞、中性粒细胞或巨噬细胞数量增加。相反，NO₂暴露减弱了烟雾诱导的TNF-α、KC和MCP-1水平的升高。NO₂的这些抑制作用可能是由于NO₂对巨噬细胞和上皮细胞产生细胞因子的调节作用，这在之前已有报道。下一步是将动物中这种联合、可控暴露的研究结果转化到人类情况中。
