Fine particulate matter (PM2.5) enhances airway hyperresponsiveness (AHR) by inducing necroptosis in BALB/c mice

Objective: To observe the effects of prolonged exposure to high concentrations of PM2.5 on the trachea and lungs of mice and to determine whether the damages to the trachea and lung are induced by necroptosis. Methods: Six- to eight-week-old female Balb/C mice of PM group were restrained in an animal restraining device using a nose-only PM2.5 online enrichment system for 8 weeks, in Shijiazhuang, Hebei, China. Anti -Fas group was exposed to PM2.5 inhalation and anti-Fas treatment via intranasal instillation. The mice in the control group inhaled filtered clean air. PM2.5 sample was collected and analyzed. Airway Hyperresponsiveness (AHR) was tested. Lung tissue and bronchoalveolar lavage fluid (BALF) were analyzed for Hematoxylin and eosin (HE) staining, electron microscopy, cellular inflammation, cytokines, Tunel, Fas, RIPK3 and MLKL expression. Results: Compared to the other two groups, PM group displayed significantly increased AHR, neutrophils in BALF, significant bronchitis and alveolar epithelial hyperplasia and inflammation and necroptosis which were indicated by increased TUNEL, Fas, RIPK3 and MLKL measure. Conclusion: Our findings suggest that PM2.5 can enhance AHR and these changes are induced by necroptosisrelated inflammation.