Diesel exhaust exposure impairs recovery of lung epithelial and cellular damage in murine model

Studies have investigated the relationship between diesel exhaust (DE) exposure and lung health, highlighting the potential for DE to induce pulmonary inflammation and oxidative stress. However, the resolution of inflammation upon withdrawal of DE exposure needs further investigation. Therefore, resolution of diesel exhaust-induced lung damage was studied in the murine model. Mice (6 weeks) were divided into three groups. Group 1 (control) mice were exposed to filtered air, Group 2 (DE) mice were exposed to DE (5.1 ± 0.7 mg/m3) & Group 3 (DE-FA) mice were exposed to DE followed by filtered air exposure. Airway hyper-responsiveness was recorded after 24 h of the last exposure. BALF and lung samples were collected for cytokine estimation, immunobiological assays, and western blot analysis. DE exposure showed an increase in lung resistance thereby causing alteration in lung function parameters (p < 0.05) which was restored in the DE-FA group. BALF analysis showed a significant increase in total cell count and protein content in DE with no resolution in DE-FA groups (p < 0.05). Lung histology showed no reduction in the bronchiolar thickness and damage in the DE-FA group suggesting irreversible lung damage (p < 0.05). The significant increase in inflammatory cytokine levels, and collagen deposition showed persistent inflammatory phase and lung damage in the DE-FA group(p < 0.05). ZO-1 was significantly decreased in both test groups indicating disintegrated lung epithelium where in claudin-5 expression showed increased lung permeability. A significant increase in neutrophil elastase activity and decreased expression of, Elafin, resulted in lung epithelial damage in the DE-FA group. Lung injury marker alpha1-antitrypsin was increased in DE-FA groups indicating an immune defense mechanism against neutrophil elastase. The study showed that DE exposure causes persistent lung damage via neutrophil elastase-associated disruption of the epithelial barrier integrity and membrane dysfunction.