ENDOTOXIN PRIMING AFFECTS THE LUNG RESPONSE TO ULTRAFINE PARTICLES AND OZONE IN YOUNG AND OLD RATS

Epidemiological studies have demonstrated a correlation between low levels of ambient particles and morbidity, particularly in the elderly with existing cardiopulmonary disease. Such correlations have been challenged due to doubts as to whether particles act alone to cause these detrimental effects. We hypothesized that ambient carbonaceous ultrafine particles (part of the urban fine particle mode) and ozone (O3) together would induce greater oxidative stress in the lung than when administered alone and that their effects would be amplified in the compromised, aging lung. We therefore exposed male F344 rats (10 wk, 20 mo) to ultrafine carbon particles (count median diameter 25 nm, 100 mug/m3, equivalent to 50 mug/m3 inhaled by humans) and to O3 (1 ppm) alone and in combination for 6 h. Low-dose endotoxin (lipopolysaccharide, LPS) priming by inhalation (70 endotoxin units estimated alveolar deposited dose) was used as a model of respiratory tract infection. Inflammatory parameters in bronchoalveolar lavage (BAL) fluid and oxidant release from BAL cells were assessed 24 h after exposure. A significant main effect of carbon, O3 and LPS on lung inflammation and a significant interaction between LPS and O3 that resulted in lower inflammation were observed in young rats. In old rats, only LPS and O3 had significant effects, but carbon and O3 interacted and increased lung inflammation above the effect level for either component alone. Oxidant release by BAL cells generally corresponded with the PMN response; however, in young rats, the combination of LPS priming with carbon and O3 exposure decreased oxidant release. In old rats, this combination increased oxidant release. These results are consistent with our hypothesis that urban ultrafine carbonaceous particles are involved in increased morbidity in sensitive populations. In addition, age and coexposure with a high level of O3 can significantly affect both lung inflammation and inflammatory cell activation such that the aged organism will experience increased oxidative stress in the lung. In both age groups, LPS enhanced the effects of particles and O3, thus allowing the observation of effects that would otherwise be masked.