Response of mouse lung to crocidolite asbestos. 2. Pulmonary fibrosis after long fibres

Our plain-English summary of Response of mouse lung to crocidolite asbestos. 2. Pulmonary fibrosis after long fibres, by I.Y. Adamson, D.H. Bowden (The Journal of Pathology, 1987).

The study

• Authors: I.Y. Adamson, D.H. Bowden
• Journal: The Journal of Pathology
• Published: 1987;152(2):109-17
• Cited by: 62 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 000292).

Abstract

To determine the cellular and fibrogenic responses of the lung to long asbestos fibres, mice were instilled intratracheally with 0.1 mg of a sample of long crocidolite fibres. Animals were killed at intervals to 20 weeks with 3H thymidine injected one h before death. Following bronchoalveolar lavage, an increase in polymorph neutrophils (PMN) and alveolar macrophages (AM) was found during the first week, accompanied by elevated glucosaminidase and alveolar protein levels. Although the PMN number dropped, some were always recovered by lavage to 20 weeks. Early multifocal necrosis of bronchiolar epithelium was followed by a large increase in labelling of epithelial cells and underlying fibroblasts. Epithelial overgrowth of luminal long fibres and inflammatory exudates was followed by giant cell and granuloma formation in the interstitium. After four weeks collagen levels were significantly increased and fibrosis was seen in these peribronchiolar locations. A few small fibres were observed in AM but no evidence of fibrosis was seen in alveolar walls. These findings suggest that injury to bronchial and bronchiolar epithelium allows long fibres to reach the interstitium where subsequent macrophage-fibroblast interactions result in a severe fibrotic reaction that resembles the bronchiolar component of human asbestosis.

In plain English

This animal experiment, from the University of Manitoba in Winnipeg, Canada, looked at how mouse lungs respond to long crocidolite asbestos fibres. The authors separated long fibres from a standard UICC crocidolite sample and placed 0.1 mg directly into the windpipes of 70 Swiss Webster mice. Control mice received water. Mice were killed at intervals up to 20 weeks. Within 24 hours the lining of the bronchi and bronchioles (the airways) was injured, with cell death that was worst at airway branch points. Inflammatory cells called neutrophils rose in lung washings and were still found at 20 weeks. The regrowing airway lining grew over fibres and debris, trapping long fibres beneath it. Giant cells appeared after one week and granulomas around the small airways by two weeks, and these became fibrotic by six weeks. A chemical measure of collagen was raised from four weeks through 20 weeks. No fibrosis was seen in the walls of the air sacs. The authors concluded that injury to the airway lining lets long fibres reach the lung tissue, where a severe fibrotic reaction follows that resembles the bronchiolar component of human asbestosis.

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 (intratracheal instillation in mice, with morphologic, cell kinetic and biochemical methods)
• Who was studied: 70 Swiss Webster mice given asbestos, plus control mice given water; animals were killed at intervals up to 20 weeks; Department of Pathology, University of Manitoba, Winnipeg, Canada
• Exposure: A single dose of 0.1 mg of long crocidolite fibres, separated from UICC crocidolite by sedimentation and suspended in 0.1 ml sterile water, instilled into the trachea. Of the fibres measured, 12 per cent were shorter than 2.5 micrometres and 73 per cent were between 2.5 and 20 micrometres.
• Main results:
  • Injury to bronchial and bronchiolar epithelium (the airway lining) was first seen within 24 hours and was maximal at airway bifurcations.
  • Neutrophils (PMN) in lavage fluid rose from zero to 2 x 10^5. The number dropped by one week, but PMN were found until the end of the 20 week period.
  • Alveolar macrophages in lavage fluid were at about twice normal values until two weeks. No macrophage contained fibres longer than 2.5 micrometres.
  • In bronchial and bronchiolar epithelial cells, uptake of the thymidine label (a measure of cell division) rose from 0.2 per cent of cells in controls to more than 12 per cent at days two and three. It stayed significantly above controls for four weeks.
  • Giant cells appeared in the tissue around the bronchioles after one week, and many granulomas had formed there by two weeks. These became more fibrotic by six weeks. Lesions containing long fibres were present for up to 20 weeks.
  • Hydroxyproline, a measure of collagen, first changed at four weeks. Total hydroxyproline in the right lung and its ratio to protein were consistently higher than in controls (p less than 0.01) through 20 weeks.
  • The alveolar epithelium (lining of the air sacs) appeared normal throughout, and no fibrosis was seen in alveolar walls.
• The authors' conclusion: The authors concluded that injury to bronchial and bronchiolar epithelium allows long fibres to reach the interstitium, where macrophage-fibroblast interactions result in a severe fibrotic reaction that resembles the bronchiolar component of human asbestosis.
• Limitations the authors state:
  • The long-fibre sample was not completely pure: some small fibres remained trapped among the long fibres, making up 12 per cent of the dose. The authors argued the airway changes were nonetheless due to the long fibres.
  • Only one dose (0.1 mg) could be tested, because a 0.5 mg dose clumped and blocked the airways.

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, Pulmonary Fibrosis, Fibrogenic, Bronchoalveolar Lavage (BAL), Alveolar Macrophage, Necrosis, Epithelium, Fibroblast.

Related studies

• Response of mouse lung to crocidolite asbestos. 1. Minimal fibrotic reaction to short fibres — I.Y. Adamson, D.H. Bowden (1987)
• Bronchiolar and alveolar lesions in the pathogenesis of crocidolite-induced pulmonary fibrosis in mice — D.H. Bowden, I.Y. Adamson (1985)
• Mesothelial cell proliferation: a nonspecific response to lung injury associated with fibrosis — I.Y. Adamson, J. Bakowska, et al. (1994)
• Mesothelial cell proliferation after instillation of long or short asbestos fibers into mouse lung — I.Y. Adamson, J. Bakowska, et al. (1993)
• Pulmonary response of mice to fiberglass: cytokinetic and biochemical studies — I.Y. Adamson, H. Prieditis, et al. (1995)
• Pulmonary reaction to long and short asbestos fibers is independent of fibroblast growth factor production by alveolar macrophages — I.Y. Adamson, D.H. Bowden (1990)

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