Effect of silica inhalation on the pulmonary clearance of a bacterial pathogen in Fischer 344 rats.
Silica inhalation predisposes workers to bacterial infection and impairments 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/m3 x 6 h/day x 5 days/wk). After 21 or 59 days of silica exposure, the rats were inoculated intratracheally with 5 x 10(3) L. monocytogenes. At 0 (noninfected controls), 3, and 7 days after infection, the left lungs were removed, homogenized, and the number of viable L. monocytogenes was counted after an overnight culture at 37 degrees C. Bronchoalveolar lavage (BAL) was performed on the right lungs. Alveolar macrophages (AM) were collected, and the AM production of chemiluminescence (CL), an index of reactive oxygen species generation, was measured. The number of lavagable neutrophils (PMNs) and acellular BAL lactate dehydrogenase (LDH) activity were determined as indices of inflammation and injury, respectively. Pre-exposure to silica for 59 days caused substantial 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. Dramatic elevations were also observed in zymosan- and phorbol myristate acetate (PMA)-stimulated CL production by lung phagocytes recovered from rats pre-exposed to silica for 59 days. These results demonstrate that short-term exposure to inhaled silica particles activates lung phagocytes, as evidenced by increases in reactive oxygen species. This up-regulation in the production of antimicrobial oxidants is likely responsible for the enhancement in pulmonary clearance of L. monocytogenes observed with short-term silica inhalation.
Antonini
J M
JM
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA.
Roberts
J R
JR
Yang
H M
HM
Barger
M W
MW
Ramsey
D
D
Castranova
V
V
Ma
J Y
JY
D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D018893:Bronchoalveolar Lavage; D015169:Colony Count, Microbial; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008088:Listeriosis / Q000276:immunology*; D008163:Luminescent Measurements; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000009:adverse effects*; D015854:Up-Regulation
D017382:Reactive Oxygen Species; D012822:Silicon Dioxide; D007770:L-Lactate Dehydrogenase