Quantitation and localization of pulmonary manganese superoxide dismutase and tumor necrosis factor a following exposure to ozone and nitrogen dioxide

Barbara L. Weller, Hanspeter Witschi, Kent E Pinkerton

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Tumor necrosis factor α (TNFα) and manganese superoxide dismutase (MnSOD) are thought to play critical roles in the process of lung injury, repair, and disease. The induction of TNFα and MnSOD were examined in a model of progressive pulmonary fibrosis along the length of the alveolar duct in rats exposed for 1, 5, and 8 weeks to a combination of 0.8 ppm ozone and 14.4 ppm nitrogen dioxide. This oxidant injury model results in a triphasic response with an initial inflammatory stage during weeks 1-3, followed by a partial resolution at weeks 4-5, and a final stage of rapidly progressive fibrosis during weeks 6-8. Changes in TNFα and MnSOD labeling for the proximal and distal alveolar ducts of the lungs were quantified using immunohistochemistry and morphometric techniques at 1, 5, and 8 weeks of exposure. A significant elevation in MnSOD was noted in alveolar macrophages and interstitial cells of the proximal and distal portions of the alveolar duct following 8 weeks of exposure. Labeling for TNFα only in the proximal region of the alveolar duct, was significantly increased in alveolar macrophages after 1 and 8 weeks of exposure, while a significant increase in TNFα labeling of interstitial cells in proximal regions was noted at all time points. We conclude that MnSOD is elevated in areas of focal injury as well as the more distal protected areas of the lungs, while TNFα correlates strongly with both the temporal and spatial aspects of greatest cellular injury in the lungs.

Original languageEnglish (US)
Pages (from-to)452-461
Number of pages10
JournalToxicological Sciences
Volume54
Issue number2
StatePublished - 2000

Keywords

  • Antioxidant
  • Cytokine
  • Fibrosis
  • Lung
  • Manganese superoxide dismutase (MnSOD)
  • Tumor necrosis factor α (TNFα)

ASJC Scopus subject areas

  • Toxicology

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