Allele-specific effects of ecSOD on asbestos-induced fibroproliferative lung disease in mice

Our plain-English summary of Allele-specific effects of ecSOD on asbestos-induced fibroproliferative lung disease in mice, by S. Jun, C.L. Fattman, B.J. Kim, et al (Free Radical Biology & Medicine, 2011).

The study

• Authors: S. Jun, C.L. Fattman, B.J. Kim, H. Jones, L. Dory
• Journal: Free Radical Biology & Medicine
• Published: 2011;50(10):1288-96
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Previous work by others suggests that there is a strain-dependent variation in the susceptibility to inflammatory lung injury in mice. Specifically, the 129/J mice appear to be more resistant to asbestos-induced pulmonary fibrosis than the C57BL/6 strain. A separate line of evidence suggests that extracellular superoxide dismutase (ecSOD) may play an important role in protecting the lung from such injuries. We have recently reported that the 129/J strain of mice has an ecSOD genotype and phenotype distinctly different from those of the C57BL/6 mice. In order to identify ecSOD as a potential "asbestos-injury resistance" gene, we bred congenic mice, on the C57BL/6 background, carrying the wild type (sod3wt) or the 129/J (sod3129) allele for ecSOD. This allowed us to examine the role of ecSOD polymorphism in susceptibility to lung injury in an otherwise identical genetic background. Interestingly, asbestos treatment induces a significant (~40%) increase in plasma ecSOD activity in the sod3129 mice, but not in the sod3wt mice. Asbestos administration results in a loss of ecSOD activity and protein from lung tissue of both congenic strains, but the lung ecSOD activity remains significantly higher in sod3129 mice. As expected, asbestos treatment results in a significant recovery of ecSOD protein in bronchoalveolar lavage fluid (BALF). The BALF of sod3129 mice also have significantly lower levels of proteins and inflammatory cells, especially neutrophils, accompanied by a significantly lower extent of lung injury, as measured by a pathology index score or hydroxyproline content. Immunohistochemistry reveals a significant loss of ecSOD from the tips of the respiratory epithelial cells in response to asbestos treatment and that the loss of immunodetectable ecSOD is compensated for by enzyme expression by infiltrating cells, especially in the sod3wt mice. Our studies thus identify ecSOD as an important anti-inflammatory gene, responsible for most, if not all of the resistance to asbestos-induced lung injury reported for the 129/J strain of mice. The data further suggest allele-specific differences in the regulation of ecSOD expression. These congenic mice therefore represent a very useful model to study the role of this enzyme in all inflammatory diseases. Polymorphisms in human ecSOD have also been reported and it appears logical to assume that such variations may have a profound effect on disease susceptibility.

Copyright © 2011 Elsevier Inc. All rights reserved.

In plain English

This was an animal experiment in mice. The authors bred congenic mice expressing either the wild-type ecSOD allele (sod3wt) or the 129/J allele (sod3129) on a 99.9% C57BL/6 background, in order to examine the role of this extracellular superoxide dismutase (ecSOD) polymorphism in an otherwise similar genetic background. Female mice aged 8 to 10 weeks received 0.1 mg NIEHS crocidolite asbestos or 0.9% saline by intratracheal instillation and were examined 14 days later. Asbestos raised plasma ecSOD level and activity by about 40% in sod3129 mice but had no effect in sod3wt mice. Lung ecSOD activity fell after asbestos in both groups but remained significantly higher in sod3129 mice. Compared with asbestos-treated sod3wt mice, asbestos-treated sod3129 mice had lower bronchoalveolar lavage fluid protein (304.0 plus or minus 30.16 micrograms versus 444.0 plus or minus 45.93), fewer inflammatory cells, a lower pathology index (2.64 plus or minus 0.21 versus 3.20 plus or minus 0.18) and less hydroxyproline. The authors concluded that ecSOD gene polymorphism modulates susceptibility to asbestos-induced lung injury in mice.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Controlled animal experiment in congenic mice carrying different ecSOD (sod3) alleles on a 99.9% C57BL/6 background, with asbestos or saline instillation and analysis 14 days later
• Who was studied: Female congenic sod3wt and sod3129 mice, 8 to 10 weeks old, 4 to 7 animals per treatment group; laboratory study at UNT Health Science Center at Fort Worth
• Exposure: Single intratracheal instillation of 0.1 mg NIEHS crocidolite asbestos (fibers longer than 10 micrometres) or 0.9% saline as control
• Main results:
  • Asbestos increased plasma ecSOD protein level and activity by about 40% in sod3129 mice, with no effect in sod3wt mice
  • After asbestos, lung ecSOD activity remained significantly higher in sod3129 mice than in sod3wt mice despite similar lung ecSOD protein amounts
  • Asbestos-treated sod3129 mice had about 30% less BALF protein and fewer total inflammatory cells than asbestos-treated sod3wt mice (protein 304.0 plus or minus 30.16 micrograms versus 444.0 plus or minus 45.93 micrograms; cells 2.16 plus or minus 0.24 x 10^6 versus 3.27 plus or minus 0.37 x 10^6)
  • The asbestos-induced rise in neutrophils, and to a lesser extent eosinophils, in BALF was markedly reduced in sod3129 mice
  • Lung pathology index after asbestos was about 20% lower in sod3129 mice (2.64 plus or minus 0.21) than in sod3wt mice (3.20 plus or minus 0.18)
  • Lung hydroxyproline after asbestos was lower in sod3129 mice (109.21 plus or minus 4.46 micrograms per lung) than in sod3wt mice (124.0 plus or minus 4.82 micrograms per lung)
  • Immunohistochemistry showed loss of intense ecSOD staining from the tips of bronchiolar epithelial cells after asbestos, with abundant ecSOD in areas infiltrated by immune cells; sod3wt lungs had more infiltrated areas than sod3129 lungs
• The authors' conclusion: The authors concluded that ecSOD gene polymorphism modulates susceptibility to asbestos-induced lung injury in mice, and that these congenic mice may serve as a model for studying ecSOD in other oxidative-stress and inflammatory diseases

Topics

Medical terms in this study, explained in our Lexicon: Pulmonary Fibrosis, Superoxide, Bronchoalveolar Lavage (BAL), Pathology, Immunohistochemistry.

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