Toxicological Sciences 70, 110-119 (2002)
Copyright © 2002 by the Society of Toxicology
RESPIRATORY TOXICOLOGY |
Residual Oil Fly Ash Increases the Susceptibility to Infection and Severely Damages the Lungs after Pulmonary Challenge with a Bacterial Pathogen
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, MS 2015, Morgantown, West Virginia 26505; and * Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115
Inhalation of residual oil fly ash (ROFA), a component of ambient particulate matter, has been shown to increase pulmonary morbidity and impair lung defense mechanisms in exposed workers. Our objective was to evaluate the effect of ROFA preexposure on lung defense and injury after pulmonary challenge with a bacterial pathogen. Male Sprague-Dawley rats were dosed intratracheally at day 0 with saline (control) or ROFA (0.2 or 1 mg/100 g body weight). Three days later, a low (5 x 103) or high (5 x 105) dose of Listeria monocytogenes was instilled intratracheally into the ROFA- and saline-treated rats. Bronchoalveolar lavage was performed on the right lungs at days 6, 8, and 10. The recovered cells were differentiated, and chemiluminescence (CL) and nitric oxide (NO) production, two indices of alveolar macrophage (AM) function, were measured. At the same time points, the left lung and spleen were removed, homogenized, and cultured, and colony-forming units were counted after an overnight incubation. Exposure to ROFA and the high dose of L. monocytogenes led to marked lung injury and inflammation as well as to an increase in mortality, compared with rats treated with saline and the high dose of L. monocytogenes. Preexposure to ROFA significantly enhanced injury and delayed the pulmonary clearance of L. monocytogenes at both bacterial doses when compared to the saline-treated control rats. ROFA had no effect on AM CL but caused a significant suppression of AM NO production, as compared to the saline control rats. We have demonstrated that acute exposure to ROFA slowed the pulmonary clearance of L. monocytogenes. The suppression in AM NO production by ROFA pretreatment likely plays an important role. These results suggest that pulmonary exposure to ROFA may alter AM function and lead to increased susceptibility to lung infection in exposed populations.
Key Words: residual oil fly ash; macrophage; Listeria monocytogenes; pulmonary clearance; chemiluminescence.
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