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...