ToxSci Advance Access originally published online on January 27, 2009
Toxicological Sciences 2009 108(1):207-221; doi:10.1093/toxsci/kfp005
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Published by Oxford University Press 2009.
Comparative Microarray Analysis and Pulmonary Changes in Brown Norway Rats Exposed to Ovalbumin and Concentrated Air Particulates
* Mail Drop 58 C Human Studies Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Mail Drop D343-03 and Mail Drop 205-01, National Center for Computational Toxicology, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan 48824
Air Quality Laboratory, University of Michigan, Ann Arbor, Michigan 48109
¶ Mail Drop B305-01 Office of the Associate Director of Health, National Health and Environmental Effects Research Laboratory Immediate Office, US Environmental Protection Agency, Office of Research and Development, Research Triangle Park, North Carolina 27711
1 To whom correspondence should be addressed at Mail Drop 58C National Health and Environmental Effects Laboratory, US Environmental Protection Agency, Office of Research and Development, Research Triangle Park, NC 27711. Express mail: 104 Mason Farm Rd. Human Study Facility, Chapel Hill, NC 27514. Fax: (919) 966-0655. E-mail: gallagher.jane{at}epa.gov.
Received October 7, 2008; accepted December 23, 2008
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Abstract |
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The interaction between air particulates and genetic susceptibility has been implicated in the pathogenesis of asthma. The overall objective of this study was to determine the effects of inhalation exposure to environmentally relevant concentrated air particulates (CAPs) on the lungs of ovalbumin (ova) sensitized and challenged Brown Norway rats. Changes in gene expression were compared with lung tissue histopathology, morphometry, and biochemical and cellular parameters in bronchoalveolar lavage fluid (BALF). Ova challenge was responsible for the preponderance of gene expression changes, related largely to inflammation. CAPs exposure alone resulted in no significant gene expression changes, but CAPs and ova-exposed rodents exhibited an enhanced effect relative to ova alone with differentially expressed genes primarily related to inflammation and airway remodeling. Gene expression data was consistent with the biochemical and cellular analyses of the BALF, the pulmonary pathology, and morphometric changes when comparing the CAPs-ova group to the air-saline or CAPs-saline group. However, the gene expression data were more sensitive than the BALF cell type and number for assessing the effects of CAPs and ova versus the ova challenge alone. In addition, the gene expression results provided some additional insight into the TGF-β–mediated molecular processes underlying these changes. The broad-based histopathology and functional genomic analyses demonstrate that exposure to CAPs exacerbates rodents with allergic inflammation induced by an allergen and suggests that asthmatics may be at increased risk for air pollution effects.
Key Words: ovalbumin; allergen; asthma; particulate matter; remodeling; inflammation; microarray.