Ramanathan Murugappan, London Nyall R, Tharakan Anuj, Surya Nitya, Sussan Thomas E, Rao Xiaoquan, Lin Sandra Y, Toskala Elina, Rajagopalan Sanjay, Biswal Shyam
1 Johns Hopkins Department of Otolaryngology-Head and Neck Surgery, Baltimore, Maryland.
2 Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Am J Respir Cell Mol Biol. 2017 Jul;57(1):59-65. doi: 10.1165/rcmb.2016-0351OC.
Exposure to airborne particulate matter (PM) has been linked to aggravation of respiratory symptoms, increased risk of cardiovascular disease, and all-cause mortality. Although the health effects of PM on the lower pulmonary airway have been extensively studied, little is known regarding the impact of chronic PM exposure on the upper sinonasal airway. We sought to test the impact of chronic airborne PM exposure on the upper respiratory system in vivo. Mice were subjected, by inhalation, to concentrated fine (2.5 μm) PM 6 h/d, 5 d/wk, for 16 weeks. Mean airborne fine PM concentration was 60.92 μm/m, a concentration of fine PM lower than that reported in some major global cities. Mice were then killed and analyzed for evidence of inflammation and barrier breakdown compared with control mice. Evidence of the destructive effects of chronic airborne PM on sinonasal health in vivo, including proinflammatory cytokine release, and macrophage and neutrophil inflammatory cell accumulation was observed. A significant increase in epithelial barrier dysfunction was observed, as assessed by serum albumin accumulation in nasal airway lavage fluid, as well as decreased expression of adhesion molecules, including claudin-1 and epithelial cadherin. A significant increase in eosinophilic inflammation, including increased IL-13, eotaxin-1, and eosinophil accumulation, was also observed. Collectively, although largely observational, these studies demonstrate the destructive effects of chronic airborne PM exposure on the sinonasal airway barrier disruption and nonallergic eosinophilic inflammation in mice.
接触空气中的颗粒物（PM）与呼吸道症状加重、心血管疾病风险增加以及全因死亡率有关。尽管PM对下呼吸道的健康影响已得到广泛研究，但关于长期接触PM对上鼻窦气道的影响却知之甚少。我们试图在体内测试长期接触空气中的PM对上呼吸道系统的影响。将小鼠通过吸入方式，每天6小时、每周5天暴露于浓缩细颗粒物（2.5μm）中，持续16周。空气中细颗粒物的平均浓度为60.92μm/m³，该细颗粒物浓度低于一些全球主要城市报道的浓度。然后将小鼠处死，并与对照小鼠相比，分析炎症和屏障破坏的证据。观察到长期接触空气中的PM对体内鼻窦健康具有破坏作用的证据，包括促炎细胞因子释放以及巨噬细胞和中性粒细胞炎症细胞积聚。通过鼻气道灌洗液中血清白蛋白的积聚评估，观察到上皮屏障功能障碍显著增加，同时包括claudin-1和上皮钙黏蛋白在内的黏附分子表达降低。还观察到嗜酸性粒细胞炎症显著增加，包括IL-13、嗜酸性粒细胞趋化因子-1增加以及嗜酸性粒细胞积聚。总体而言，尽管这些研究主要是观察性的，但它们证明了长期接触空气中的PM对小鼠鼻窦气道屏障破坏和非过敏性嗜酸性粒细胞炎症具有破坏作用。
