Asbestos-induced autoimmunity in C57BL/6 mice

Our plain-English summary of Asbestos-induced autoimmunity in C57BL/6 mice, by J.C. Pfau, J.J. Sentissi, S. Li, et al (Journal of Immunotoxicology, 2008).

The study

• Authors: J.C. Pfau, J.J. Sentissi, S. Li, L. Calderon-Garciduenas, J.M. Brown, D.J. Blake
• Journal: Journal of Immunotoxicology
• Published: 2008;5(2):129-37
• Cited by: 42 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Environmental impacts on autoimmunity have significant public health implications. Epidemiological studies have shown associations between exposure to airborne silicates, such as crystalline silica or asbestos, and autoimmunity, but the etiology remains unclear. The purpose of this study was to test the hypothesis that asbestos could lead to a specific pattern of autoantibodies and pathology indicative of systemic autoimmune disease (SAID). Female C57Bl/6 mice were instilled intratracheally with 2 doses x 60 microg/mouse of amphibole asbestos (tremolite), wollastonite (a non-fibrogenic control fiber), or saline alone. Serum samples were collected and urine was checked for protein bi-weekly for 7 months. By 26 weeks, the asbestos-instilled animals had a significantly higher frequency of positive anti-nuclear antibody (ANA) tests compared to wollastonite and saline groups. The majority of positive ANAs showed homogeneous or combined homogeneous/speckled patterns, and tested positive for antibodies to dsDNA and SSA/Ro 52. Serum isotyping showed no significant changes in IgM, IgA, or IgG subclasses. However, there was an overall decrease in the mean IgG serum concentration in asbestos-instilled mice. IgG immune complex deposition was demonstrated in the kidneys of asbestos-instilled mice, with evidence of glomerular and tubule abnormalities suggestive of glomerulonephritis. Flow cytometry demonstrated moderate changes in the percentages of CD25+ T-suppressor cells and B1a B-cells in the superficial cervical lymph nodes of the asbestos-instilled mice. These data demonstrate that asbestos leads to immunologic changes consistent with the development of autoimmunity. This study provides a non-autoimmune prone murine model for use in future elucidation of mechanisms involved in asbestos-induced autoimmune disease.

In plain English

This animal experiment tested whether amphibole asbestos could induce autoimmunity in a mouse strain the authors describe as not autoimmune-prone. Female C57Bl/6 mice received two intratracheal instillations one week apart: 60 µg per dose of Korean tremolite or of wollastonite (a non-fibrogenic control fiber), or saline alone, with 10 mice per group followed for seven months. By 26 weeks the asbestos-instilled mice had a significantly higher frequency of positive antinuclear antibody (ANA) tests than the wollastonite and saline groups. Five of seven tremolite mice and no saline mice had anti-dsDNA antibodies, a difference the authors reported as not statistically significant given the small sample. Antibodies to SSA/Ro p52 were increased (p less than 0.01 versus saline). Ninety percent of tremolite mice had kidney IgG and C3 deposition. The authors also described glomerular damage in these mice without giving a count, and test strips showed no increased urine protein. Total serum IgG fell in tremolite mice. In superficial cervical lymph nodes the percentage of CD4+ CD25+ T-cells decreased, which the authors said might reflect a loss of regulatory T-cells.

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 (mouse) experiment with intratracheal fiber instillation and 7 months of follow-up
• Who was studied: Female 8-week-old C57Bl/6 mice, 10 per treatment group (some assays used 7 mice per group), at The University of Montana-Missoula
• Exposure: Two intratracheal doses of 60 µg each, one week apart, of Korean tremolite amphibole asbestos (NIST) or wollastonite (NYCO, a non-fibrogenic control fiber), compared with saline alone
• Main results:
  • Higher frequency of positive ANA tests in the asbestos (tremolite) group than in the wollastonite and saline groups by 26 weeks (n = 7 mice/group, p less than 0.05)
  • Anti-dsDNA antibodies in 5 of 7 tremolite-instilled mice and none of the saline mice; the authors state this difference was not statistically significant
  • Antibodies to the p52 subunit of SS-A/Ro were identified in tremolite-instilled mice by blot and ELISA; p less than 0.01 compared with saline, and wollastonite was not significantly different from saline
  • IgG and complement C3 deposition in the kidneys of 90% of tremolite-instilled mice (n=10), with little or none in saline or wollastonite mice
  • No increased urine protein was detected by the test-strip method
  • Kidney histology of tremolite-instilled mice showed glomerular damage and signs of tubular regeneration; no count of affected mice was given
  • Superficial cervical lymph nodes of treated mice were enlarged with increased cell numbers; percentages of total T- and B-cells were not significantly altered
  • In superficial cervical lymph nodes, the percentage of CD4+ CD25+ T-cells decreased, which the authors said might represent a loss of regulatory T-cells; the increase in CD5+ (B1a) B-cells was not statistically significant (n = 7)
  • Total serum IgG decreased in tremolite-treated mice; IgA, IgE, IgM and IgG subclasses were statistically unchanged (n=7)
• The authors' conclusion: The authors concluded that tremolite asbestos led to antinuclear antibody production, kidney immune complex deposition and kidney pathology consistent with their hypothesis. They also concluded that this strain provides a non-autoimmune-prone murine model for future study of mechanisms.
• Limitations the authors state:
  • The anti-dsDNA difference was not statistically significant because of the small number of samples
  • Low-level positive ANA tests in control animals may reflect the low screening dilution, ageing, or the surgical instillation itself
  • Intratracheal instillation was used rather than inhalation; the authors call it not ideal and plan a comparison with inhalation exposure
  • The tremolite sample is only one component of the amphibole mixture now described for Libby vermiculite
  • The meaning of the CD4+ CD25+ T-cell change is uncertain without FoxP3 phenotyping
  • Further work is needed to define the location and extent of the kidney immune complexes and the time course of glomerulonephritis

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

The National Library of Medicine indexes this study under subjects our site covers: Tremolite.

Medical terms in this study, explained in our Lexicon: Silicate, Crystalline, Etiology, Pathology, Amphibole Asbestos, Tremolite, Wollastonite, Fibrogenic.

Related studies

• Erionite induces production of autoantibodies and IL-17 in C57BL/6 mice — C.N. Zebedeo, C. Davis, et al. (2014)
• Autoantibodies from mice exposed to Libby amphibole asbestos bind SSA/Ro52-enriched apoptotic blebs of murine macrophages — D.J. Blake, S.A. Wetzel, et al. (2008)
• Amphibole, but not chrysotile, asbestos induces anti-nuclear autoantibodies and IL-17 in C57BL/6 mice — A. Ferro, C.N. Zebedeo, et al. (2014)
• Prevalence of anti-nuclear autoantibodies in subjects exposed to natural asbestiform fibers: a cross-sectional study — C. Ledda, R. Caltabiano, et al. (2018)
• Silicosis and autoimmunity — S. Lee, H. Hayashi, et al. (2017)
• Late Inflammation Induced by Asbestiform Fibers in Mice Is Ameliorated by a Small Molecule Synthetic Lignan — R. Badger, K. Park, et al. (2021)

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