Submitted on August 4, 2005
Accepted on February 24, 2006
Duodenal Cytochrome b: a Novel Ferri-reductase in Airway Epithelial Cells
Jennifer L Turi1*, Xinchao Wang2, Andrew T McKie3, Eva Nozik-Grayck4, Lisa B Mamo1, Kay Crissman2, Claude A Piantadosi5, and Andrew J Ghio2
1 Departments of Pediatrics, Duke University Medical Center, Durham, NC, USA
2 National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park, NC, USA
3 Department of Molecular Medicine, Guy's, King's and St. Thomas' School of Medicine, King's College, London, United Kingdom
4 Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado, USA
5 Department of Medicine, Duke University Medical Center, Durham, NC, USA
* To whom correspondence should be addressed. E-mail: turi0002{at}mc.duke.edu.
Catalytically active iron in the lung causes oxidative stress and promotes microbial growth which can be limited by intracellular sequestration of iron within ferritin. Because cellular iron uptake requires membrane ferri-reductase activity that in the gut can be provided by duodenal cytochrome b (Dcytb), we sought Dcytb in the lung to test the hypothesis that it contributes to epithelial iron regulation by reducing Fe3+ for cellular iron transport. Dcytb expression was found in respiratory epithelium in vitro and in vivo and was responsive to iron concentration. Iron transport was measured in human bronchial epithelial (HBE) cells using inductively coupled plasma atomic emission spectroscopy and was demonstrated to be partially inhibited in the presence of Dcytb blocking antibody, suggesting that Dcytb reduces Fe3+ for cellular iron transport. A definite source of reducing equivalents for Dcytb was sought but not identified. We found no evidence that ascorbate was involved, but did demonstrate that O2- production decreased when Dcytb function was blocked. The presence of Dcytb in airway epithelial cells and its regulation by iron therefore, may contribute to pulmonary cyto-protection.
