Harkema Jack R, Hotchkiss Lucas A, Vetter Nicholas A, Jackson-Humbles Daven N, Lewandowski Ryan P, Wagner James G
1 Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Toxicol Pathol. 2017 Jan;45(1):161-171. doi: 10.1177/0192623316674274. Epub 2016 Nov 15.
Ozone is an irritating gas found in photochemical smog. Epidemiological associations have been made between the onset of asthma and childhood exposures to increasing levels of ambient ozone (i.e., air pollutant-induced nonatopic asthma). Individuals, however, vary in their susceptibility to this outdoor air pollutant, which may be due, in part, to their genetic makeup. The present study was designed to test the hypothesis that there are murine strain-dependent differences in pulmonary and nasal pathologic responses to repeated ozone exposures. C57BL/6NTac and BALB/cNTac mice were exposed to 0 or 0.8 ppm ozone, 4 hr/day, for 9 consecutive weekdays. In both strains of mice, ozone induced eosinophilic inflammation and mucous cell metaplasia in the nasal and pulmonary airways. Lungs of ozone-exposed C57BL/6NTac mice, however, had greater eosinophilic inflammation, mucous cell metaplasia, and expression of genes related to type 2 immunity and airway mucus hypersecretion, as compared to similarly exposed BALB/cNTac mice. Ozone-exposed C57BL/6NTac mice also had greater eosinophilic rhinitis but a similar degree of mucous cell metaplasia in nasal epithelium, as ozone-exposed BALB/cNTac mice. These findings suggest that nonatopic individuals may differ in their inflammatory and epithelial responses to repeated ozone exposures that are due, in part, to genetic factors.
臭氧是一种存在于光化学烟雾中的刺激性气体。流行病学研究已发现哮喘的发作与儿童时期暴露于环境中不断增加的臭氧水平之间存在关联（即空气污染物诱发的非特应性哮喘）。然而，个体对这种室外空气污染物的易感性各不相同，这可能部分归因于他们的基因构成。本研究旨在验证以下假设：对反复暴露于臭氧的肺部和鼻腔病理反应存在小鼠品系依赖性差异。将C57BL/6NTac和BALB/cNTac小鼠连续9个工作日每天4小时暴露于0或0.8 ppm的臭氧中。在这两种品系的小鼠中，臭氧均诱发了鼻腔和肺部气道的嗜酸性粒细胞炎症和黏液细胞化生。然而，与同样暴露于臭氧的BALB/cNTac小鼠相比，暴露于臭氧的C57BL/6NTac小鼠的肺部有更严重的嗜酸性粒细胞炎症、黏液细胞化生以及与2型免疫和气道黏液高分泌相关的基因表达。暴露于臭氧的C57BL/6NTac小鼠也有更严重的嗜酸性粒细胞性鼻炎，但鼻腔上皮的黏液细胞化生程度与暴露于臭氧的BALB/cNTac小鼠相似。这些发现表明，非特应性个体对反复暴露于臭氧的炎症和上皮反应可能存在差异，这部分归因于遗传因素。
