Pulmonary inflammatory response to inhaled ultrafine particles is modifiedby age, ozone exposure, and bacterial toxin

Epidemiological studies demonstrate associations between increasing levels of ambient particles and morbidity in the elderly with cardiopulmonary dise ase. Such findings have been challenged partly because particles may not ac t alone to cause these effects. We hypothesized that carbonaceous ambient u ltrafine particles and ozone can act together to induce greater oxidative s tress and inflammation in the lung than when administered alone and that th ese effects would be amplified in the compromised, aging lung. Two models o f a compromised lung were used: endotoxin priming and old-age emphysema (T- SK mice). Young (10 wk) and old (22 mo) male F344 rats and male T-SK mice ( 14-17 mo) were exposed to ultrafine carbon particles (count median diameter 25 nm, 110 mug/m(3)) and to ozone (1 ppm) alone and in combination for 6 h . inhalation of low-dose endotoxin (70 and 7.5 units estimated alveolar dep osited dose in rats and mice, respectively) was used to model respiratory-t ract infection. Cellular and biochemical lavage parameters and oxidant rele ase from lung lavage cells were assessed 24 h after exposure. Inflammatory cell influx into the alveolar space was observed for both species and age g roups: The combination of inhaled ultrafine carbon and ozone after endotoxi n priming resulted in the greatest increase in lavage-fluid neutrophils. In general, the unstimulated and stimulated release of reactive oxygen specie s (ROS) from lavage inflammatory cells correlated well with the neutrophil response. There were significant effects of carbon particles as well as a c onsistent interaction between carbon and ozone as determined by analysis of variance (ANOVA). However this interaction was in the opposite direction i n young rats versus old rats and old T-SK mice: Carbon and ozone interacted such that ROS activity was depressed in young rats, whereas it was enhance d in old rats and old T-SK mice, indicating age-dependent functional differ ences in elicited pulmonary inflammatory cells. These results demonstrate t hat ultrafine carbonaceous particles inhaled for short periods of time can induce significant pulmonary inflammation and oxidative stress that are mod ified by age, copollutants, and a compromised respiratory tract.