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Am J Physiol Lung Cell Mol Physiol 292: L134-L143, 2007. First published August 11, 2006; doi:10.1152/ajplung.00534.2005
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Lung injury after ozone exposure is iron dependent

¹National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, and ³National Institute of Environmental Health Sciences and National Toxicology Program, Research Triangle Park; ²Department of Pediatrics, Duke University Medical Center, Durham, North Carolina; and ⁴Department of Biochemistry, State University of New York, Buffalo, New York

Submitted 19 December 2005 ; accepted in final form 1 August 2006

We tested the hypothesis that oxidative stress and biological effect after ozone (O₃) exposure are dependent on changes in iron homeostasis. After O₃ exposure, healthy volunteers demonstrated increased lavage concentrations of iron, transferrin, lactoferrin, and ferritin. In normal rats, alterations of iron metabolism after O₃ exposure were immediate and preceded the inflammatory influx. To test for participation of this disruption in iron homeostasis in lung injury following O₃ inhalation, we exposed Belgrade rats, which are functionally deficient in divalent metal transporter 1 (DMT1) as a means of iron uptake, and controls to O₃. Iron homeostasis was disrupted to a greater extent and the extent of injury was greater in Belgrade rats than in control rats. Nonheme iron and ferritin concentrations were higher in human bronchial epithelial (HBE) cells exposed to O₃ than in HBE cells exposed to filtered air. Aldehyde generation and IL-8 release by the HBE cells was also elevated following O₃ exposure. Human embryonic kidney (HEK 293) cells with elevated expression of a DMT1 construct were exposed to filtered air and O₃. With exposure to O₃, elevated DMT1 expression diminished oxidative stress (i.e., aldehyde generation) and IL-8 release. We conclude that iron participates critically in the oxidative stress and biological effects after O₃ exposure.

air pollution; lung diseases; ferritin; oxidants; free radicals

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