Bronchiolar and alveolar lesions in the pathogenesis of crocidolite-induced pulmonary fibrosis in mice

Our plain-English summary of Bronchiolar and alveolar lesions in the pathogenesis of crocidolite-induced pulmonary fibrosis in mice, by D.H. Bowden, I.Y. Adamson (The Journal of Pathology, 1985).

The study

• Authors: D.H. Bowden, I.Y. Adamson
• Journal: The Journal of Pathology
• Published: 1985;147(4):257-67
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestosis is generally considered to result in restrictive pulmonary disease associated with interstitial fibrosis. Recently, however, attention has focused upon bronchiolar lesions and concomitant obstruction to air flow. The responses of conducting airways and alveoli were studied over a 20 week period following instillation of crocidolite to mice. The location of the lesions and the sequential inflammatory changes were studied by bronchoalveolar lavage, light and electron microscopy; regenerative activity was monitored by autoradiographs. Within 48 h there was multifocal necrosis of bronchiolar epithelium, maximal at bifurcations where longer fibres tend to adhere. Subsequently, intralumenal exudates were overgrown by epithelium and incorporated into the bronchiolar connective tissue where active peribronchiolar granulomas persisted until 20 weeks. Alveolar lesions were located predominantly in peribronchiolar air sacs and at the junctions of bronchioles and alveolar ducts. Focal acute injury of type 1 cells and transepithelial passage facilitated transport of short asbestos fibres to the interstitium where they were phagocytozed by macrophages. Regenerative activity was prompt with active division of type 2 epithelial cells. Biochemically, collagen increased after 4 weeks, when fibrosis was predominantly located in the bronchiolar lumens and in peribronchiolar connective tissue with lesser amounts in the centrilobular alveolar interstitium. The results suggest that the longer fibres induce bronchiolar injury and a more severe fibrotic pattern similar to the recently described changes seen in human asbestosis.

In plain English

The authors placed 1 mg of UICC crocidolite reference asbestos (78 per cent of fibres shorter than 5 micrometres) into the windpipes of 70 male Swiss Webster mice. Control mice received sterile water. Groups of four were killed at intervals from 1 day to 20 weeks. Lungs were studied by washing, microscopy, labelling of dividing cells and collagen measurement. Airway injury was consistently more severe than air-sac injury. Within 48 hours, patches of airway lining died, mostly at branching points where larger fibres tended to stick. The lining regrew over the debris. Granulomas formed by 10 weeks, became progressively scarred, and still contained fibres at 20 weeks. In the air sacs, mainly those near the airways, short fibres injured lining cells; some crossed into the lung tissue, where macrophages took them up. Collagen was significantly higher in exposed mice from 4 weeks, reaching two to three times control values at 20 weeks. The authors suggested that the longer fibres caused the airway injury and a more severe scarring pattern similar to that recently described in 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: single intratracheal instillation of crocidolite in mice, with lungs examined at intervals up to 20 weeks
• Who was studied: 70 male Swiss Webster mice, killed in groups of four at days 1, 2, 3, 5, 7 and 10 and at weeks 2, 4, 6, 8, 10, 12, 16 and 20. Control mice were injected with sterile water; their number is not stated. The work was done at the Pathology Department, University of Manitoba, Winnipeg, Canada. Study dates are not given.
• Exposure: UICC crocidolite reference sample, a mixture of short and long fibres in which 78 per cent of fibres were less than 5 micrometres long. Each mouse received a single dose of 1 mg suspended in 0.1 ml sterile water, placed directly into the windpipe.
• Main results:
  • In the crocidolite-treated mice, lesions occurred in both the conducting airways and the air sacs, and airway injury was consistently the more severe.
  • Within the first 48 hours, there was multifocal death of the lining of the bronchi and bronchioles. It was greatest at branching points, where the larger fibres tended to stick.
  • By 2 weeks, regrowing airway lining had covered the inflammatory material, and macrophages and fibres were incorporated into the connective tissue around the airways.
  • Granulomas with multinucleated giant cells were established around the airways by 10 weeks. They became progressively fibrosed, but giant cells and asbestos fibres were still present at 20 weeks.
  • In lung washings from treated mice, polymorphonuclear leukocytes (PMN) made up 72 per cent of cells at day 1 and 50 per cent at 1 week. By 3 weeks, macrophages made up more than 80 per cent of cells.
  • Air-sac lesions in the first 48 hours were mainly in air sacs near the bronchioles and at the junctions of terminal bronchioles and alveolar ducts. Most alveoli at the periphery of the lung were free of fibres and unchanged.
  • Some type 1 alveolar lining cells were acutely injured and contained small fibres. Type 2 cells contained no fibres and were not necrotic, and they began dividing between 2 and 5 days.
  • Small fibres that crossed the type 1 lining were found inside interstitial macrophages. Fibroblasts later multiplied at these sites, and collagen was often found near macrophages containing fibres.
  • Fibrosis was found mainly in the bronchial lumen and in the tissue around the airways and in the alveolar interstitium.
  • Hydroxyproline (a measure of collagen) in the right lung was significantly higher in asbestos-treated mice than in controls from 4 weeks onwards. It rose steadily to two to three times control values at 20 weeks.
• The authors' conclusion: The authors suggested that the longer fibres cause the bronchiolar injury and a more severe fibrotic pattern, similar to recently described changes in human asbestosis. They reasoned that because only very short fibres were seen in the alveoli, long fibres were likely responsible for the bronchiolar necrosis.

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, Interstitial Fibrosis, Alveoli, Bronchoalveolar Lavage (BAL), Necrosis, Epithelium, Exudate.

Related studies

• Response of mouse lung to crocidolite asbestos. 2. Pulmonary fibrosis after long fibres — I.Y. Adamson, D.H. Bowden (1987)
• Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis — I. Lemaire, H. Beaudoin, et al. (1986)
• Alveolar macrophage cytokine and growth factor production in a rat model of crocidolite-induced pulmonary inflammation and fibrosis — K.E. Driscoll, J.K. Maurer, et al. (1995)
• Incorporation of tritiated thymidine by epithelial and interstitial cells in bronchiolar-alveolar regions of asbestos-exposed rats — A.R. Brody, L.H. Overby (1989)
• Mitochondrial catalase overexpressed transgenic mice are protected against lung fibrosis in part via preventing alveolar epithelial cell mitochondrial DNA damage — S.J. Kim, P. Cheresh, et al. (2016)
• Response of mouse lung to crocidolite asbestos. 1. Minimal fibrotic reaction to short fibres — I.Y. Adamson, D.H. Bowden (1987)

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