ToxSci Advance Access published online on January 27, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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, NC 27711, USA heidenfelder.brooke{at}epa.gov and hudgens.edward{at}epa.gov
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, NC 27711, USA reif.david{at}epa.gov and hubal.elaine{at}epa.gov
Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA bramble2{at}cvm.msu.edu and wagnerja{at}msu.edu and harkemaj{at}cvm.msu.edu
Air Quality Laboratory, University of Michigan, Ann Arbor, MI 48109, USA tomoko{at}umich.edu and jkeeler{at}umich.edu
¶ 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, NC 27711, USA Edwards.stephen{at}epa.gov
* Corresponding author: Jane Gallagher, 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 Email: gallagher.jane{at}epa.gov Phone: (919) 966-0638 Fax: (919) 966-0655
Received October 7, 2008; revision received December 18, 2008; accepted December 23, 2008
 |
Abstract |
|---|
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 to 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 was 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 TGFβ 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.