Acute ozone exposure results in airway epithelial and immune cell disturbances in mice

Elevated levels of ambient ozone (O₃), a criteria air pollutant produced by industries and automobiles, are significantly correlated with increased respiratory morbidity. Acute O₃ exposure disrupts airway epithelial integrity, compromising lung function and aggravating existing lung diseases. Despite prior work, the detailed kinetics of O₃-induced acute lung injury and resolution remain unclear.

To delineate the temporal progression and resolution of O₃-induced acute lung injury in mice, we exposed eight-week-old female mice to filtered air or 1.5 ppm O3 for 4h and assessed lung injury markers at 12h, 36h, 60h, 108h, and 204h post-exposure.

Analysis of bronchoalveolar lavage fluid (BALF) revealed that neutrophil counts peaked at 12h and protein concentration at 36h, followed by a progressive decrease from 60h to baseline levels at 204h. The acute O₃ exposure also induced time-dependent alterations in multiple cytokines, including eotaxin, G-CSF, KC, MIP-1α, MIP-1β, IL-5, IL-6, IL-12, and MCP-1. At 12h post-exposure, severe denudation of airway epithelial cells was observed. Basal cell proliferation peaked between 36h and 60h, while ciliated cell restoration began at 60h, with normal epithelial composition achieved by 204h.

This study elucidates the temporal sequence of events in O₃-induced acute lung injury, demonstrating a progression from initial epithelial damage and inflammatory cell infiltration to subsequent epithelial regeneration and inflammation resolution over 204h. These findings provide important insights into the kinetics of O₃-induced acute lung injury and repair mechanisms.