Dynamics of Inflammatory and Pathological Changes Induced by Single Exposure of Particulate Matter (PM_2.5) in Mice:...

Chronic Obstructive Pulmonary Disease (COPD) is a progressive disorder of lungs marked by chronic bronchitis and emphysema. Particulate matter (PM_2.5), a major component of air pollution has been correlated with COPD incidence. The present work aimed to understand dynamics of cellular/molecular players behind PM_2.5-mediated COPD pathogenesis in mice by conducting dose and time-course studies. Single intratracheal exposure of PM_2.5 at a dose of either 100 or 200 μg induced inflammatory response in lungs at 4 days. Time course studies showed that inflammation once triggered by PM_2.5 is progressive in nature as reflected by data on BALF inflammatory cells at 7/14 days. Similarly, various cytokines/chemokines (KC/IL-6/TNF-α/IL-1β/G-CSF/MCP-1) peak at either 7 or 14 days. However, inflammation declined sharply at 21 days. Data on LPO/GSH and activities of SOD/Catalase show induction of continuous oxidative stress in lung tissue. Next, enhanced mtROS in the CD11b⁺ inflammatory cells confirms the redox imbalance in neutrophils/macrophages. A continuous decline in lung function was observed till 28 days. Further, histological analysis of lung tissues at 28 days confirmed the presence of emphysematous lesions, validating the potency of PM_2.5 to cause irreversible damage to lungs through complex interplay of various cellular/molecular players which may be exploited as potential preventive/therapeutic targets.