Deficiency in the divalent metal transporter 1 increases bleomycin-induced lung injury

Funmei Yang, Jacqueline G. Stonehuerner, Judy H. Richards, Ngoc Bich Nguyen, Kimberly D. Callaghan, David J. Haile, Andrew J. Ghio

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Exposure to bleomycin can result in an inflammatory lung injury. The biological effect of this anti-neoplastic agent is dependent on its coordination of iron with subsequent oxidant generation. In lung cells, divalent metal transporter 1 (DMT1) can participate in metal transport resulting in control of an oxidative stress and tissue damage. We tested the postulate that metal import by DMT1 would participate in preventing lung injury after exposure to bleomycin. Microcytic anemia (mk/mk) mice defective in DMT1 and wild-type mice were exposed to either bleomycin or saline via intratracheal instillation and the resultant lung injury was compared. Twentyfour h after instillation, the number of neutrophils and protein concentrations after bleomycin exposure were significantly elevated in the mk/mk mice relative to the wild-type mice. Similarly, levels of a pro-inflammatory mediator were significantly increased in the mk/mk mice relative to wild-type mice following bleomycin instillation. Relative to wild-type mice, mk/mk mice demonstrated lower non-heme iron concentrations in the lung, liver, spleen, and splenic, peritoneal, and liver macrophages. In contrast, levels of this metal were elevated in alveolar macrophages from mk/mk mice. We conclude that DMT1 participates in the inflammatory lung injury after bleomycin with mk/mk mice having increased inflammation and damage following exposure. This finding supports the hypothesis that DMT1 takes part in iron detoxification and homeostasis in the lung.

Original languageEnglish (US)
Pages (from-to)657-667
Number of pages11
JournalBioMetals
Volume23
Issue number4
DOIs
StatePublished - Aug 1 2010

Keywords

  • Ferritin
  • Iron
  • Lung diseases
  • Mouse

ASJC Scopus subject areas

  • Biomaterials
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Metals and Alloys

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    Yang, F., Stonehuerner, J. G., Richards, J. H., Nguyen, N. B., Callaghan, K. D., Haile, D. J., & Ghio, A. J. (2010). Deficiency in the divalent metal transporter 1 increases bleomycin-induced lung injury. BioMetals, 23(4), 657-667. https://doi.org/10.1007/s10534-010-9326-0