Pulmonary response of mice to fiberglass: cytokinetic and biochemical studies

Our plain-English summary of Pulmonary response of mice to fiberglass: cytokinetic and biochemical studies, by I.Y. Adamson, H. Prieditis, C. Hedgecock (Journal of Toxicology and Environmental Health, 1995).

The study

• Authors: I.Y. Adamson, H. Prieditis, C. Hedgecock
• Journal: Journal of Toxicology and Environmental Health
• Published: 1995;46(4):411-24
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

It has been suggested that glass fibers in the respirable size range may pose a health hazard similar to asbestos because of the similarities in physical characteristics. To compare the pulmonary cell response with that described earlier with crocidolite asbestos, we administered a milled fiberglass sample to mice by intratracheal instillation. Little effect was seen at a dose of 0.1 mg, but at 1 mg there was epithelial injury and an inflammatory cell response concentrated at bronchiolar-alveolar duct regions. Cellular incorporation of tritiated thymidine showed that repair of both bronchiolar and alveolar epithelium occurred rapidly. This was followed by an extended increase in cell labeling, particularly in peribronchiolar fibroblasts, from 2 to 8 wk after fiber instillation. Granulomas formed at this site and later there was morphologic evidence of fibrosis, which was confirmed biochemically by a significant increase in lung collagen at 4-16 wk. Although 10 times higher dose is required, the results show that the lung response to fiberglass in this experimental system is similar to that described previously for crocidolite asbestos; the sites of cell injury and repair are the same, and the subsequent fibrotic response produces small airway disease.

In plain English

In this animal experiment, the authors placed milled fiberglass (mean fiber length 5.2 micrometers) into the windpipes of male Swiss Webster mice. The aim was to compare the lung response with their earlier crocidolite asbestos findings. Asbestos was not tested in this study. A 0.1 mg trial dose caused only brief, mild inflammation and no fibrosis. Then 50 mice received 1 mg and were killed in groups of four at intervals up to 16 weeks. Control mice received sterile water. After 1 mg, inflammatory cells and protein in lung washings stayed above controls for up to 8 weeks. Injury centered where small airways meet the alveolar ducts, where longer fibers settled, and early lining damage was quickly repaired. Granulomas formed around small airways after 2 weeks and appeared more fibrotic by 8 weeks; no further progression was apparent, though granulomas persisted to 16 weeks. Lung hydroxyproline, a collagen measure, was significantly above controls after 4 weeks. The authors concluded that the response resembled their earlier crocidolite findings but needed a 10 times higher dose. They noted their dose and route were not "physiologic."

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: a single dose of fiberglass placed directly into the trachea (intratracheal instillation) of mice, followed over time, with control animals given sterile water
• Who was studied: 50 male Swiss Webster mice given fiberglass, killed in groups of four at days 3, 7 and 10 and weeks 2, 4, 6, 8, 12 and 16. Control mice were injected with 0.1 ml sterile water. The study was done at the Department of Pathology, University of Manitoba, Winnipeg, Canada. Study dates are not stated.
• Exposure: Milled glass microfibers from Johns-Manville, size-separated by sedimentation. Mean fiber length was 5.2 micrometers: 47% under 2.5, 25% at 2.5 to 5, 17.5% at 5 to 10, 7% at 10 to 20, and 3.5% over 20 micrometers. The main study used a 1 mg dose in 0.1 ml sterile water; a 0.1 mg dose was used in trial experiments.
• Main results:
  • At 0.1 mg fiberglass, only a brief, mild inflammatory response was seen. Lungs appeared normal after 2 weeks and no fibrosis developed.
  • After 1 mg fiberglass, alveolar macrophages in lung washings increased threefold and stayed above normal for 8 weeks
  • After 1 mg fiberglass, polymorphonuclear leukocytes in lung washings increased rapidly and in large numbers
  • Protein in lung washings, a sign of injury to the air-blood barrier, rose sixfold at 3 days after fiberglass and was significantly higher than controls for the following 8 weeks
  • Lung hydroxyproline (a measure of collagen) in fiberglass-treated mice was significantly higher than in age-matched controls after 4 weeks
  • The ratio of hydroxyproline to total protein in fiberglass-treated mice rose at 2 weeks and stayed above controls for the rest of the experiment
  • The lung response occurred mainly in the bronchiolar-alveolar duct regions
  • At 3 days, death of the lining cells of the terminal bronchioles was seen
  • Bronchial and bronchiolar lining cells showed a rapid peak of DNA synthesis consistent with early repair. In controls, 0.1 to 0.2% of these cells were labeled.
  • Granulomas formed around the bronchioles after 2 weeks and appeared more fibrotic by 8 weeks. There appeared to be no further progression of disease, although the granulomas persisted up to 16 weeks.
  • There was little evidence of fibrotic change in the alveolar walls at any time
  • Labeling of other lung cells (control values about 0.3%) was significantly above normal for 8 weeks after fiberglass. After 2 weeks, the main labeled cell type was the fibroblast.
• The authors' conclusion: The authors concluded that 1 mg fiberglass produced lung changes similar to those they had earlier described after 0.1 mg crocidolite asbestos in the same mouse strain, but that a much higher dose of glass fiber was required.
• Limitations the authors state:
  • Intratracheal instillation delivers a large single dose that is unevenly distributed
  • The dose level and route of administration were not "physiologic"
  • Fiber diameters likely differed between the glass and asbestos samples, so fiber numbers could not be compared precisely

Topics

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

Medical terms in this study, explained in our Lexicon: Crocidolite, Epithelium, Fibroblast, Granuloma, Fibrosis, Collagen.

Related studies

• Comparative pulmonary responses to inhaled inorganic fibers with asbestos and fiberglass — K.P. Lee, C.E. Barras, et al. (1981)
• Response of mouse lung to crocidolite asbestos. 2. Pulmonary fibrosis after long fibres — I.Y. Adamson, D.H. Bowden (1987)
• Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study — B.N. Snyder-Talkington, C. Dong, 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)
• Bronchiolar and alveolar lesions in the pathogenesis of crocidolite-induced pulmonary fibrosis in mice — D.H. Bowden, I.Y. Adamson (1985)
• In vivo pulmonary toxicity of cellulose in rats — E. Tátrai, M. Brozik, et al. (1996)

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