Laboratory of experimental and molecular immunology and neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, University of Orleans, F-45071, Orleans-Cedex2, France.
Artimmune SAS, Orléans, France.
Sci Rep. 2018 Jul 13;8(1):10611. doi: 10.1038/s41598-018-28261-9.
Environmental air pollutants including ozone cause severe lung injury and aggravate respiratory diseases such as asthma and COPD. Here we compared the effect of ozone on respiratory epithelium injury, inflammation, hyperreactivity and airway remodeling in mice upon acute (1ppm, 1 h) and chronic exposure (1.5ppm, 2 h, twice weekly for 6 weeks). Acute ozone exposure caused respiratory epithelial disruption with protein leak and neutrophil recruitment in the broncho-alveolar space, leading to lung inflammation and airway hyperresponsiveness (AHR) to methacholine. All these parameters were increased upon chronic ozone exposure, including collagen deposition. The structure of the airways as assessed by automatic numerical image analysis showed significant differences: While acute ozone exposure increased bronchial and lumen circularity but decreased epithelial thickness and area, chronic ozone exposure revealed epithelial injury with reduced height, distended bronchioles, enlarged alveolar space and increased collagen deposition, indicative of peribronchiolar fibrosis and emphysema as characterized by a significant increase in the density and diameter of airspaces with decreased airspace numbers. In conclusion, morphometric numerical analysis enables an automatic and unbiased assessment of small airway remodeling. The structural changes of the small airways correlated with functional changes allowing to follow the progression from acute to chronic ozone induced respiratory pathology.
环境空气污染物，包括臭氧，会导致严重的肺部损伤，并加重哮喘和 COPD 等呼吸道疾病。在这里，我们比较了臭氧对急性（1ppm，1 小时）和慢性（1.5ppm，2 小时，每周两次，共 6 周）暴露后小鼠呼吸道上皮损伤、炎症、高反应性和气道重塑的影响。急性臭氧暴露导致呼吸上皮破裂，支气管肺泡空间出现蛋白渗漏和中性粒细胞募集，导致肺部炎症和对乙酰甲胆碱的气道高反应性。所有这些参数在慢性臭氧暴露时都会增加，包括胶原沉积。通过自动数值图像分析评估气道结构显示出显著差异：急性臭氧暴露增加了支气管和管腔的圆形度，但减少了上皮的厚度和面积，而慢性臭氧暴露则显示出上皮损伤，支气管高度降低，细支气管扩张，肺泡空间增大，胶原沉积增加，提示小气道纤维化和肺气肿，表现为气道密度和直径显著增加，气道数量减少。总之，形态计量学的数值分析可以实现对小气道重塑的自动和无偏评估。小气道的结构变化与功能变化相关，允许我们从急性到慢性臭氧诱导的呼吸道病变的进展进行跟踪。
