Toxicological Sciences 72, 331-338 (2003)
Copyright © 2003 by the Society of Toxicology
RESPIRATORY TOXICOLOGY |
Effect of Preexposure to Ultrafine Carbon Black on Respiratory Syncytial Virus Infection in Mice
CIIT Centers for Health Research, 6 Davis Drive, P. O. Box 12137, Research Triangle Park, North Carolina 27709-2137
Epidemiological studies have indicated that exposure to elevated levels of particulate matter exacerbates several pulmonary diseases, including asthma, bronchitis, and viral infections. Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in infants and may lead to the development of asthma in childhood. To determine whether particle exposure modulates the immune response to RSV, eight-week-old female BALB/c mice received an intratracheal (i.t.) instillation of either 40 µg ultrafine carbon black (CB) particles or vehicle. The following day, mice were i.t. instilled with either 106 pfu RSV or uninfected media. End points were examined 1, 2, 4, 7, and 10 days during RSV infection. Compared with RSV alone, tumor necrosis factor-
(TNF-
) protein was reduced in the bronchoalveolar lavage fluid (BALF) on days 1 and 2 of infection; there was also a reduction in BALF lymphocyte numbers on day 4, which correlated with reductions in both IFN-
-inducible protein (IP-10), lymphotactin, and IFN-
mRNAs in the lungs of RSV + CB mice. Multiprobe ribonuclease protection assays of RSV + CB lung tissue showed no changes in the RSV-associated chemokines regulated upon activation, normal T cell expressed and secreted (RANTES), eotaxin, monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP)-1
or MIP-1ß. Viral titers in RSV + CB mice were lower than RSV on days 24 of infection. By day 7 of infection, however, neutrophil numbers, proinflammatory cytokine mRNA expression, and protein levels of TNF-
and the Th2 cytokine interleukin (IL)-13 were increased in the lungs of RSV + CB mice, indicating an exacerbation of infection. These data indicate that preexposure to ultrafine particles induces an inflammatory milieu promoting allergic immune responses rather than IFN
production necessary for microbial defense.
Key Words: RSV; chemokine; cytokine; ultrafine particles; alveolar macrophages; lymphocytes; mouse; ribonuclease protection assay.
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A. L. Lambert, J. B. Mangum, M. P. DeLorme, and J. I. Everitt Ultrafine Carbon Black Particles Enhance Respiratory Syncytial Virus-Induced Airway Reactivity, Pulmonary Inflammation, and Chemokine Expression Toxicol. Sci., April 1, 2003; 72(2): 339 - 346. [Abstract] [Full Text] [PDF] |
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