Collagen accumulation over time in the murine lung after exposure to crocidolite asbestos or Libby amphibole

Our plain-English summary of Collagen accumulation over time in the murine lung after exposure to crocidolite asbestos or Libby amphibole, by A.M. Smartt, M. Brezinski, M. Trapkus, et al (Environmental Toxicology, 2010).

The study

• Authors: A.M. Smartt, M. Brezinski, M. Trapkus, D. Gardner, E.A. Putnam
• Journal: Environmental Toxicology
• Published: 2010;25(1):68-76
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Libby, MT is the site of a closed vermiculite mine that produced ore contaminated with asbestos-like amphiboles. Worldwide distribution of the material and the long latency period for manifestation of asbestos-related diseases (ARDs) has created a significant health threat for many years to come. The composition of the Libby material [termed the Libby amphibole (LA)] differs from other well-studied types of asbestos in that it is a mixture of several amphibole fibers. The purpose of this study was to determine the fibrotic effects of LA exposure in a mouse model and to compare these effects to those of a well-characterized amphibole fiber, crocidolite asbestos. We exposed C57Bl/6 mice to LA or crocidolite and analyzed lung RNA, protein, and morphology at 1 week, 1 month, and 3 months post instillation. Our results indicate that both forms of amphibole studied induced increased collagen types I and III mRNA expression and collagen protein deposition in exposed murine lungs compared to the PBS-instilled control lungs, and that these collagen increases were the most significant at 1 month after exposure. However, crocidolite-exposed mice demonstrated greater increases in collagen deposition than those exposed to LA, indicating that the fibrotic effects of LA exposure, although not as severe as those of crocidolite in this model system, were still able to induce collagen deposition.

In plain English

This was a laboratory study in mice comparing Libby amphibole (LA), a mineral mixture from the Libby, Montana vermiculite mine, with crocidolite asbestos. Male and female C57Bl/6 mice, 8 to 10 per treatment group, had 100 micrograms of LA or crocidolite, or salt solution alone as a control, placed directly into the windpipe. Lungs were examined 1 week, 1 month and 3 months later for inflammation, collagen gene activity and collagen (scar-tissue protein) content. Compared with controls, both fibers raised type I collagen gene activity and lung collagen. The authors reported that the collagen increases were most significant at 1 month. LA's effects on lung tissue appeared less severe than crocidolite's at every time point. Inflammation was significantly above control levels only in crocidolite-exposed mice, and only at 1 month. At 3 months, lung collagen in LA-exposed mice was not significantly different from controls. No pleural changes suggesting mesothelioma were seen, which the authors said would be unexpected so soon. The authors concluded that LA's fibrotic reaction did not reach crocidolite's level in the same period. They noted that the mouse model may imperfectly represent human disease.

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: Animal experiment (mice given fibers by intratracheal instillation, with lungs examined at three time points)
• Who was studied: Pathogen-free male and female C57Bl/6 mice, 6 to 8 weeks old, with 8 to 10 mice per treatment group, studied at the University of Montana. Study dates are not given.
• Exposure: A single intratracheal dose of 100 micrograms of crocidolite asbestos or Libby amphibole (LA) in 30 microliters of sterile saline (PBS). Control mice received saline only. The article describes LA as a mix of amphibole fibers and cleavage fragments including tremolite, actinolite, soda tremolite, richterite and winchite. The LA sample was supplied by the U.S. Geological Survey.
• Main results:
  • Under the microscope, LA-exposed lungs showed effects similar to crocidolite-exposed lungs, but less severe at all time points.
  • Crocidolite-exposed mice had average inflammation scores of 1.2 (minimal) at 1 week and 1.8 (mild) at 1 month.
  • LA-exposed mice scored 0.9 at 1 week, 0.7 at 1 month and 0.4 at 3 months (minimal inflammation). Their inflammation did not appear to worsen over time.
  • Inflammation was significantly increased compared with saline controls only in crocidolite-treated mice, and only at 1 month.
  • Pro-collagen 1A1 (type I collagen) mRNA was increased over saline controls in both the crocidolite and LA groups at 1 week and 1 month. The authors reported it returned to baseline over time.
  • Type III collagen (Col3A1) mRNA was significantly increased at 1 month in LA-treated mice (P less than 0.05). The increase at that time point in crocidolite-treated mice was not statistically significant.
  • Lung collagen content, measured as hydroxyproline, was significantly higher than in saline controls at 1 week in both the crocidolite and LA groups (P less than 0.05).
  • The authors reported that the collagen increases in exposed lungs were most significant at 1 month after exposure.
  • At 3 months, lung hydroxyproline in LA-treated mice was not significantly different from saline controls. The article reports that crocidolite-treated mice remained significantly higher than controls (P less than 0.01).
  • No pleural changes suggesting possible mesothelioma were detected. The authors noted this would be unexpected over such short time frames.
• The authors' conclusion: The authors concluded that both fibers induced fibrosis in mouse lungs. They found that the fibrotic reaction to LA did not reach the level induced by crocidolite over the same time course, which they considered expected given LA's mixed mineral composition.
• Limitations the authors state:
  • The authors stated that the mouse model may be an imperfect representation of the human disease.
  • Pleural disease predominates in people exposed to LA, but the mice showed no observable pleural changes. The authors suggested this could reflect differences in route or duration of exposure, or in latency.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Libby vermiculite mine, Montana

All asbestos mines

Topics

Medical terms in this study, explained in our Lexicon: Collagen, Crocidolite, Libby amphiboles, vermiculite, Amphibole Group, Latency, Deposition.

Related studies

• Libby amphibole-induced mesothelial cell autoantibodies bind to surface plasminogen and alter collagen matrix remodeling — R. Hanson, C. Evilia, et al. (2016)
• Libby amphibole-induced mesothelial cell autoantibodies promote collagen deposition in mice — J. Gilmer, K. Serve, et al. (2016)
• A novel method for accurate collagen and biochemical assessment of pulmonary tissue utilizing one animal — C.R. Kliment, J.M. Englert, et al. (2011)
• Iron mobilization from crocidolite as enhancer of collagen content in rat lung fibroblasts — C. Gardi, P. Calzoni, et al. (1997)
• A protective role for T lymphocytes in asbestos-induced pulmonary inflammation and collagen deposition — E. Corsini, M.I. Luster, et al. (1994)
• Internalization of Libby amphibole asbestos and induction of oxidative stress in murine macrophages — D.J. Blake, C.M. Bolin, et al. (2007)

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