Ozone impairs endogenous compensatory responses in allergic asthma.
Ozone impairs endogenous compensatory responses in allergic asthma.
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DOI：
10.1016/j.taap.2022.116341
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发表时间：
2022-12
影响因子：
3.8
通讯作者：
K. Ho;D. Weimar;Gina Torres-Matias;Hyunwook Lee;Saaleha Shamsi;E. Shalosky;Michael Yaeger;Hannah Hartzler-Lovins;K. Dunigan-Russell;Daria Jelic;Caymen M. Novak;K. Gowdy;J. Englert;M. Ballinger
中科院分区：
文献类型：
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作者：
K. Ho;D. Weimar;Gina Torres-Matias;Hyunwook Lee;Saaleha Shamsi;E. Shalosky;Michael Yaeger;Hannah Hartzler-Lovins;K. Dunigan-Russell;Daria Jelic;Caymen M. Novak;K. Gowdy;J. Englert;M. Ballinger
Asthma is a chronic inflammatory airway disease characterized by acute exacerbations triggered by inhaled allergens, respiratory infections, or air pollution. Ozone (O3), a major component of air pollution, can damage the lung epithelium in healthy individuals. Despite this association, little is known about the effects of O3and its impact on chronic lung disease. Epidemiological data have demonstrated that elevations in ambient O3are associated with increased asthma exacerbations. To identify mechanisms by which O3exposure leads to asthma exacerbations, we developed a two-hit mouse model where mice were sensitized and challenged with three common allergens (dust mite, ragweed and Aspergillus fumigates, DRA) to induce allergic inflammation prior to exposure to O3(DRAsingle bondO3). Changes in lung physiology, inflammatory cells, and inflammation were measured. Exposure to O3following DRA significantly increased airway hyperreactivity (AHR), which was independent of TLR4. DRA exposure resulted in increased BAL eosinophilia while O3exposure resulted in neutrophilia. Additionally, O3exposure following DRA blunted anti-inflammatory and antioxidant responses. Finally, there were significantly less monocytes and innate lymphoid type 2 cells (ILC2s) in the dual challenged DRA-O3group suggesting that the lack of these immune cells may influence O3-induced AHR in the setting of allergic inflammation. In summary, we developed a mouse model that mirrors some aspects of the clinical course of asthma exacerbations due to air pollution and identified that O3exposure in the asthmatic lung leads to impaired endogenous anti-inflammatory and antioxidant responses and alterations inflammatory cell populations.
