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Inhalation Toxicology
International Forum for Respiratory Research
Volume 22, 2010 - Issue sup2: Air Pollution and Health
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AAAR Supplement

Age specific responses to acute inhalation of diffusion flame soot particles: Cellular injury and the airway antioxidant response

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Pages 70-83 | Received 17 Jun 2010, Accepted 02 Aug 2010, Published online: 21 Oct 2010
 

Abstract

Current studies of particulate matter (PM) are confounded by the fact that PM is a complex mixture of primary (crustal material, soot, metals) and secondary (nitrates, sulfates, and organics formed in the atmosphere) compounds with considerable variance in composition by sources and location. We have developed a laboratory-based PM that is replicable, does not contain dust or metals and that can be used to study specific health effects of PM composition in animal models. We exposed both neonatal (7 days of age) and adult rats to a single 6-h exposure of laboratory generated fine diffusion flame particles (DFP; 170 µg/m3), or filtered air. Pulmonary gene and protein expression as well as indicators of cytotoxicity were evaluated 24 h after exposure. Although DFP exposure did not alter airway epithelial cell composition in either neonates or adults, increased lactate dehydrogenase activity was found in the bronchoalveolar lavage fluid of neonates indicating an age-specific increase in susceptibility. In adults, 16 genes were differentially expressed as a result of DFP exposure whereas only 6 genes were altered in the airways of neonates. Glutamate cytsteine ligase protein was increased in abundance in both DFP exposed neonates and adults indicating an initiation of antioxidant responses involving the synthesis of glutathione. DFP significantly decreased catalase gene expression in adult airways, although catalase protein expression was increased by DFP in both neonates and adults. We conclude that key airway antioxidant enzymes undergo changes in expression in response to a moderate PM exposure that does not cause frank epithelial injury and that neonates have a different response pattern than adults.

Acknowledgements

We are grateful to the following people for their skilled technical assistance during exposures, sample collection and processing: Brian Tarkington, Louise Olson, Patricia Edwards, Judy Shimizu, and Trenton Combs. We thank Michael Kleeman’s laboratory at UC Davis for EC/OC sample analysis and Barbara Zielinska at DRI for filter PAH speciation. Finally, we acknowledge Kent Pinkerton, Michael Kleeman and Jesse Charrier for reading and editing the manuscript.

Declaration of interest

Support for the University of California at Davis core facilities used in this work: the Cellular and Molecular Imaging Core Facility (ES005707) and the inhalation exposure facility at the California National Primate Research Center (RR00169) is acknowledged. Although the research described in the article has been funded primarily by the United States Environmental Protection Agency through grant RD-83241401-0 to the University of California, Davis, it has not been subject to the Agency’s required peer and policy review and, therefore, does not necessarily reflect the views of the Agency and no official endorsement should be inferred. The project described was also supported in part by Award Number P42ES004699 from the National Institute of Environmental Health Sciences. Ms. Sutherland’s effort was supported by a National Institute of Environmental Health Sciences training grant T32 ES007059. Mr. Chan’s effort was partially supported by a traineeship with the Superfund Basic Sciences Research Program at UC Davis (P42 ES04699). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Environmental Health Sciences or the National Institutes of Health.

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