Effect of silica inhalation on the pulmonary clearance of a bacterial pathogen in fischer 344 rats

Silica inhalation predisposes workers to bacterial infection and impairment s in pulmonary defense function. In this study, we evaluated the effect of pre-exposure to silica on lung defense mechanisms by use of a rat pulmonary Listeria monocytogenes infection model. Male Fischer 344 rats were exposed by inhalation to filtered air or silica (15 mg/m(3) x 6 h/day x 5 days/wk) . After 21 or 59 days of silica exposure, the rats were inoculated intratra cheally with 5 x 10(3) L. monocytogenes. At 0 (noninfected controls), 3, an d 7 days after infection, the left lungs were removed, homogenized, and the number of viable L. monocytogenes was counted after an overnight culture a t 37 degrees C. Bronchoalveolar lavage (BAL) was pet-formed on the right lu ngs. Alveolar macrophages (AM) were collected, and the AM production of che miluminescence (CL), an index of reactive oxygen species generation, was me asured. The number of lavagable neutrophils (PMNs) and acellular BAL lactat e dehydrogenase (LDH) activity were determined as indices of inflammation a nd injury, respectively. Pre-exposure to silica for 59 days caused substant ial increases in PMN number and LDH activity compared with the air controls , whereas silica inhalation for both 21 and 59 days significantly enhanced the pulmonary clearance of L. monocytogenes compared with air controls. Dra matic elevations were also observed in zymosan and phorbol myristate acetat e (PMA)stimulated CL production by lung phagocytes recovered from rats pre- exposed to silica for 59 days. These results demonstrate that short-term ex posure to inhaled silica particles activates lung phagocytes, as evidenced by increases in reactive oxygen species. This up-regulation in the producti on of antimicrobial oxidants is likely responsible for the enhancement in p ulmonary clearance oft. monocytogenes observed with short-term silica inhal ation.