Age, Strain, and Gender as Factors for Increased Sensitivity of the Mouse Lung to Inhaled Ozone

Ozone (O-3) is a respiratory irritant that leads to airway inflammation and pulmonary dysfunction. Animal studies show that neonates are more sensitive to O-3 inhalation than adults, and children represent a potentially susceptible population. This latter notion is not well established, and biological mechanisms underlying a predisposition to pollution-induced pulmonary effects are unknown. We examined age and strain as interactive factors affecting differential pulmonary responses to inhaled O-3. Male and female adult mice (15 weeks old) and neonates (15-16 days old) from eight genetically diverse inbred strains were exposed to 0.8 ppm O-3 for 5 h. Pulmonary injury and lung inflammation were quantified as total protein concentration and total polymorphonuclear neutrophil (PMN) number in lavage fluid recovered 24-h postexposure. Dose-response and time-course curves were generated using SJL/J pups, and O-18 lung burden dose was assessed in additional mice. Interstrain differences in response to O-3 were seen in neonatal mice: Balb/cJ and SJL/J being most sensitive and A/J and 129x1/SvJ most resistant. The PMN response to O-3 was greater in neonates than in adults, specifically for SJL/J and C3H/HeJ strains, independent of dose. Small gender differences were also observed in adult mice. Variation in protein concentrations and PMN counts between adults and pups were strain dependent, suggesting that genetic determinants do play a role in age-related sensitivity to O-3. Further research will help to determine what genetic factors contribute to these heightened responses, and to quantify the relative contribution of genes vs. environment in O-3-induced health effects.