Response of mouse lung to crocidolite asbestos. 1. Minimal fibrotic reaction to short fibres

Our plain-English summary of Response of mouse lung to crocidolite asbestos. 1. Minimal fibrotic reaction to short 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):99-107
• Cited by: 44 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. 000291).

Abstract

To determine the relationship between the development of pulmonary fibrosis and the size of deposited asbestos, we prepared a pure sample of short crocidolite fibres and instilled 0.5 mg of 0.1 mg to the lungs of mice. Animals were killed up to 20 weeks later with 3H thymidine injected 1 h before death. By bronchoalveolar lavage, there was a rapid transient increase in polymorph neutrophils (PMN) and in glucosaminidase levels; alveolar macrophage (AM) numbers were elevated in the 0.5 mg group for eight weeks. Most fibres were phagocytized by AM, many of which were heavily laden and cleared from the lung over the 20 week period. Some fibres were seen in type 1 epithelial cells, frequently associated with cell injury. From cell kinetic studies, a very brief proliferative response was seen in bronchiolar epithelial and Type 2 alveolar epithelial cells. A greater response was seen in interstitial fibroblasts which showed increased labelling up to two weeks after 0.5 mg asbestos. However no granulomas were seen and very little fibrosis was found by morphology or by biochemistry at any time after 0.5 mg; no fibrosis was seen after instilling 0.1 mg. The results show that a high dose of exclusively short asbestos fibres produces minimal lung injury and fibrosis in spite of long standing macrophage-fibre interaction in the alveoli.

In plain English

This was an animal experiment from the University of Manitoba, Winnipeg, on how mouse lungs respond to short crocidolite asbestos fibres. The authors separated short fibres from a standard UICC crocidolite sample. These had a mean length of 0.6 micrometres, and 98.8 per cent were shorter than 2.5 micrometres. Doses of 0.5 mg or 0.1 mg were placed into the windpipes of male Swiss Webster mice, which were killed in groups of four from 1 day to 20 weeks later. Control mice received sterile water. Neutrophils, a type of inflammatory cell, rose briefly and were near zero by five days. Alveolar macrophages, which took up most fibres, were significantly raised from 5 days to eight weeks after 0.5 mg, and fibre-laden macrophages were still recovered at 20 weeks. No granulomas were seen. After 0.5 mg, total hydroxyproline, a measure of collagen, was significantly higher than in controls (p less than 0.05) only at eight and 20 weeks. After 0.1 mg it did not differ from controls. The authors concluded that the short fibres produced little or no lung fibrosis.

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 of short crocidolite fibres in mice, with lavage, microscopy, cell-labelling and biochemical measurements at intervals up to 20 weeks
• Who was studied: Male Swiss Webster mice at the Department of Pathology, University of Manitoba, Winnipeg, Canada. The article states each asbestos sample was instilled into 70 mice. Groups of four were killed at days 1, 2, 3, 5, 7 and 10 and at weeks 2, 4, 6, 8, 10, 12, 16 and 20. Control mice received sterile water. No experiment dates are given.
• Exposure: Short crocidolite fibres separated by sedimentation from UICC crocidolite. Mean length was 0.6 micrometres, and 98.8 per cent of fibres were under 2.5 micrometres. Two doses were given: 0.5 mg and 0.1 mg.
• Main results:
  • Neutrophils (PMN) recovered by lavage rose from near zero in controls to 1 x 10^6 after 0.5 mg and to 3 x 10^5 after 0.1 mg. They were near zero by five days.
  • Alveolar macrophage numbers were significantly higher than controls between 5 days and eight weeks after 0.5 mg. After 0.1 mg they were only slightly higher, between one and two weeks.
  • Asbestos-laden macrophages were recovered by lavage throughout the 20 weeks, although their number and fibre content decreased.
  • Glucosaminidase activity and protein in lavage fluid were raised only in the first week after 0.5 mg.
  • After both doses, labelling of bronchial and bronchiolar epithelial cells rose to about 3 per cent and returned to normal by five days.
  • Labelling of the other lung cells reached more than 2 per cent, against 0.3 per cent in controls. After 0.5 mg it did not return to normal for two weeks.
  • After 0.5 mg, the main increase in labelling was in interstitial cells, most of them fibroblasts, and lasted until two weeks. After 0.1 mg, labelling returned to normal by five days.
  • Hydroxyproline did not differ from controls after 0.1 mg. After 0.5 mg, the hydroxyproline-to-protein ratio rose slightly at 4 to 8 weeks, and total hydroxyproline was significantly higher (p less than 0.05) only at eight and 20 weeks.
  • No giant cells or granulomas were seen at any time in either dose group. No fibrosis was found in the 0.1 mg group.
  • In the 0.5 mg group, slight focal thickening of alveolar walls lasted until the end of the experiment. Some collagen was deposited near interstitial macrophages containing fibres.
• The authors' conclusion: The authors concluded that a pure sample of short asbestos fibres, which reached almost only the alveoli, caused little or no lung fibrosis, with almost all particles taken up and cleared by alveolar macrophages. They judged it unlikely that the granulomas and extensive interstitial fibrosis seen after asbestos exposure in humans or animals can be attributed to fibres shorter than 2.5 micrometres.

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, Bronchoalveolar Lavage (BAL), Alveolar Macrophage, Interstitial, Fibroblast, Granuloma, Fibrosis.

Related studies

• Response of mouse lung to crocidolite asbestos. 2. Pulmonary fibrosis after long 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)
• 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)
• Mesothelial cell proliferation after instillation of long or short asbestos fibers into mouse lung — I.Y. Adamson, J. Bakowska, et al. (1993)
• Mesothelial cell proliferation: a nonspecific response to lung injury associated with fibrosis — I.Y. Adamson, J. Bakowska, et al. (1994)
• Characterization of the bronchoalveolar cellular response in experimental asbestosis. Different reactions depending on the fibrogenic potential — I. Lemaire (1985)

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