Dynamics of Inflammatory and Pathological Changes Induced by Single Exposure of Particulate Matter (PM2.5) in Mice: Potential Implications in COPD

Chronic Obstructive Pulmonary Disease (COPD) is a progressive disorder of lungs marked by chronic bronchitis and emphysema. Particulate matter (PM2.5), a major component of air pollution has been correlated with COPD incidence. The present work aimed to understand dynamics of cellular/molecular players behind PM2.5-mediated COPD pathogenesis in mice by conducting dose and time-course studies. Single intratracheal exposure of PM2.5 at a dose of either 100 or 200 mu g induced inflammatory response in lungs at 4 days. Time course studies showed that inflammation once triggered by PM2.5 is progressive in nature as reflected by data on BALF inflammatory cells at 7/14 days. Similarly, various cytokines/chemokines (KC/IL-6/TNF-alpha/IL-1 beta/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 PM2.5 to cause irreversible damage to lungs through complex interplay of various cellular/molecular players which may be exploited as potential preventive/therapeutic targets.