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Epidemiological studies demonstrate associations between increasing levels of ambient particles and morbidity in the elderly with cardiopulmonary disease. Such findings have been challenged partly because particles may not act alone to cause these effects. Wehypothesized that carbonaceous ambient ultrafine particles and ozone can act together to induce greater oxidative stress and inflammation in the lung than when administered alone and that these effects would be amplified in the compromised, aging lung. Two models of a compromised lung were used: endotoxin priming and old-age emphysema (TSK mice). Young (10 wk) and old (22 mo) male F344 rats and male TSK mice (14-17 mo) were exposed to ultrafine carbon particles (count median diameter 25 nm, 110 µg/m[sup 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 deposited dose in rats and mice, respectively) was used to model respiratorytract infection. Cellular and biochemical lavage parameters and oxidant release from lung lavage cells were assessed 24 h after exposure. Inflammatory cell influx into the alveolar space was observed for both species and age groups: The combination of inhaled ultrafine carbon and ozone after endotoxin priming resulted in the greatest increase in lavage-fluid neutrophils. In general, the unstimulated and stimulated release of reactive oxygen species (ROS) from lavage inflammatory cells correlated well with the neutrophil response. There were significant effects of carbon particles as wellas a consistent interaction between carbon and ozone as determined by analysis of variance (ANOVA). However, this interaction was in the opposite direction in young rats versus old rats and old TSK mice: Carbon and ozone interacted such that ROS activity was depressed in young rats, whereas it was enhanced in old rats and old TSK mice, indicating age-dependent functional differences in elicited pulmonary inflammatory cells. These results demonstrate that ultrafine carbonaceous particles inhaled for short periods of time can induce significant pulmonary inflammation and oxidative stress that are modified by age, copollutants, and a compromised respiratory tract. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS) is a component of the gram-negative bacterial cell wall that is known to activate inflammatory cells and enhance the production of inflammatory mediators in the lung. As it is a ubiquitous compound, inhalation exposure is highly likely in the human environment. Adaptation is a phenomenon by which a previous exposure results in improved survival or reduced injury as compared to a single exposure alone. We hypothesized that the basic proinflammatory effects of LPS in the lung could result in the development of adaptation in animals. Based on evidence of age- and species-related differences in lung injury, we used an acute lung injury model with inhaled LPS to compare the development of adaptation in young and old Fisher 344 rats and C57Bl/6J mice. Animals were exposed to low-dose (predicted lung deposition 20 ng in rats and 5 ng in mice) LPS aerosols for 10 min on 3 consecutive days; on day 4, a high dose (rats 200 ng; mice 25 ng) was delivered. Another group of animals received only the high LPS dose on day 4, whereas controls were unexposed. Twenty-four hours after the last exposure, cellular and inflammatory parameters in bronchoalveolar lavage (BAL) were determined. An adaptive response was found in both rats and mice. Adapted animals showed significantly fewer BAL neutrophils compared to nonadapted ones; there was also a significantly lower release of oxidants from phorbol methyl ester-stimulated BAL cells from adapted compared to nonadapted animals, which, in turn, showed a greater response than controls. Furthermore, studies in old animals (21 mo of age) showed that adaptation also occurs in this age group. The adaptive response is clear in old mice; in rats, there is greater variability in the response, but an adaptive trend is apparent. Therefore, we have demonstrated that inhaled low-dose LPS can induce adaptation to subsequent higher doses, much as has been shown for other toxicants that induce oxidative lung injury. [ABSTRACT FROM AUTHOR]

Provides a corrected reprint to the article previously published in the 2000 issue of the journal 'Inhalation Toxicology.'