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 existi ng cardiopulmonary disease. Such correlations have been challenged due to d oubts as to whether particles act alone to cause these detrimental effects. We hypothesized that ambient carbonaceous ultrafine particles (part of the urban fine particle model and ozone (O-3) together would induce greater ox idative stress in the lung than when administered alone and that their effe cts 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 mu g/m(3), equivalent to 50 mu g/m(3) inhaled by humans ) and to O-3 (1 ppm) alone and in combination for 6 h. low-dose endotoxin ( lipopolysaccharide, LPS) priming by inhalation (70 endotoxin units estimate d alveolar deposited dose) was used as a model of respiratory tract infecti on. inflammatory parameters in bronchoalveolar lavage (BAL) fluid and oxida nt release from BAL cells were assessed 24 h after exposure. A significant main effect or carbon, O-3 and LPS on lung inflammation and a significant i nteraction between LPS and O-3 that resulted in lower inflammation were obs erved in young rats. In old rats, only IFS and O-3 had significant effects, but carbon and O-3 interacted and increased lung inflammation above the ef fect level for either component alone. Oxidant release by BAL cells general ly corresponded with the PMN response; however, in young rats, the combinat ion of IFS priming with carbon and O-3 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 O-3 can significantly affect both l ung inflammation and inflammatory cell activation such that the aged organi sm will experience increased oxidative stress in the lung. In both age grou ps, LPS enhanced the effects of particles and O-3, thus allowing the observ ation of effects that would otherwise be masked.