Resistance of hypotransferrinemic mice to hyperoxia-induced lung injury

Funmei Yang, Jacqueline J. Coalson, Heather H. Bobb, Jacqueline D. Carter, Jameela Banu, Andrew J. Ghio

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32 Scopus citations

Abstract

Oxidative stress plays a central role in the pathogenesis of acute and chronic pulmonary diseases. Safe sequestration of iron, which participates in the formation of the hydroxyl radical, is crucial in the lung's defense. We used a mouse line defective in the major iron transport protein transferrin to investigate the effect of aberrant iron metabolism on the lung's defense against oxidative injury. The tolerance to hyperoxic lung injury was greater in the hypotransferrinemic than in wild-type mice as documented by histopathology and biochemical indexes for lung damage. There was no increase in the levels of intracellular antioxidants, inflammatory cytokines, and heme oxygenase-1 in the hypotransferrinemic mouse lung compared with those in wild-type mice. However, there were elevated expressions of ferritin and lactoferrin in the lung of hypotransferrinemic mice, especially in the alveolar macrophages. Our results suggest that pulmonary lactoferrin and ferritin protect animals against oxidative stress, most likely via their capacity to sequester iron, and that alveolar macrophages are the key participants in iron detoxification in the lower respiratory tract.

Original languageEnglish (US)
Pages (from-to)L1214-L1223
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume277
Issue number6 21-6
StatePublished - Dec 1 1999

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Keywords

  • Antioxidants
  • Ferritin
  • Iron metabolism
  • Lactoferrin
  • Transferrin

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Yang, F., Coalson, J. J., Bobb, H. H., Carter, J. D., Banu, J., & Ghio, A. J. (1999). Resistance of hypotransferrinemic mice to hyperoxia-induced lung injury. American Journal of Physiology - Lung Cellular and Molecular Physiology, 277(6 21-6), L1214-L1223.