Mesothelial cell proliferation after instillation of long or short asbestos fibers into mouse lung

Our plain-English summary of Mesothelial cell proliferation after instillation of long or short asbestos fibers into mouse lung, by I.Y. Adamson, J. Bakowska, D.H. Bowden (The American Journal of Pathology, 1993).

The study

• Authors: I.Y. Adamson, J. Bakowska, D.H. Bowden
• Journal: The American Journal of Pathology
• Published: 1993;142(4):1209-16
• Cited by: 45 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

The relationship of asbestos deposition in the lung to subsequent cell proliferation at the pleural surface is not clear. The present study examines DNA synthesis by various pulmonary cells, particularly those at the pleura after intratracheal injection of 0.1 mg crocidolite to mice using: 1) long fibers (> 20 mu), which are deposited in bronchiolar regions and induce fibrosis; 2) short fibers (< 1 mu), which reach alveoli but do not induce fibrosis. Mice also received 2 microCi/g tritiated thymidine 1 hour before death at intervals to 16 weeks. Short fibers induced only a small increase in labeling of bronchiolar epithelial and interstitial cells, which subsided by 5 days, when a small increase in labeled mesothelial and subpleural cells was seen. In contrast, long fibers damaged the bronchiolar epithelium and became incorporated into connective tissue. During regeneration, 12% of cells were labeled at 3 days and labeling was greater than controls to 4 weeks. Increased peribronchiolar labeling of fibroblasts and interstitial macrophages was seen around long fibers, and increased DNA synthesis by mesothelial and subpleural cells was found. Up to 2% of mesothelial cells were labeled 1 week after long fibers compared to near zero in controls. No long fibers were found at the pleura. Activation of interstitial macrophages in response to long crocidolite fibers is associated with fibroblast proliferation. It is now suggested that mesothelial cells may also be stimulated by cytokines from activated interstitial macrophages that diffuse across the interstitium, without requiring actual fiber translocation to the pleura.

In plain English

In this animal experiment, the authors placed 0.1 mg of crocidolite asbestos into the windpipes of male Swiss Webster mice. They used either long fibers (average 24.4 microns) or short fibers (average 0.6 microns), and control mice received sterile water. Mice were killed at intervals up to 16 weeks, and dividing cells were counted using a radioactive label. Short fibers caused only small, brief increases in cell division and no lung fibrosis. Long fibers caused fibrosis and longer-lasting increases in dividing cells. This included mesothelial cells at the pleura, which rose from near zero in controls to over 2% at 1 week and stayed above control levels until week 4. No long fibers were seen at the pleura, and no plaques or mesotheliomas were found at 16 weeks. The authors suggested that cytokines released by interstitial macrophages responding to the fibers might stimulate pleural cells without fibers reaching the pleura. They said the single exposure, the dose or the limited observation period may explain why mesotheliomas did not develop.

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 intratracheal instillation of long or short crocidolite fibers in mice, with controls given sterile water, examined at intervals up to 16 weeks
• Who was studied: Male Swiss Webster mice: 70 per asbestos sample, killed in groups of four at days 1, 2, 3, 5 and 7 and weeks 2, 4, 8, 12 and 16. Control mice were killed at selected times. The work was done at the Department of Pathology, University of Manitoba, Winnipeg, Canada.
• Exposure: Standard UICC crocidolite asbestos separated into long fibers (mean length 24.4 microns) and short fibers (mean 0.6 microns), each given as a single 0.1 mg dose. The same weight meant a much larger number of short fibers.
• Main results:
  • Bronchial and bronchiolar epithelial cell labeling after short fibers rose from a control level of 0.2% to 1.7% at 1 day and was normal by 5 days.
  • Bronchial and bronchiolar epithelial cell labeling after long fibers rose to over 12% and stayed above normal for 4 weeks.
  • Labeling of other lung cells averaged 0.3% in controls. It rose briefly to about 0.7% at day 3 after short fibers. After long fibers it peaked at over 3% at 1 week and did not return to the control range for 4 weeks.
  • After long fibers, labeling of subpleural cells (mostly fibroblasts) increased sixfold by 1 week. After short fibers there was only a brief, small increase.
  • After long fibers, labeling of mesothelial cells rose from a near zero control value to over 2% at 1 week and did not fall to control values until week 4. Short fibers produced only a small increase at day 5.
  • Long fibers were never seen in the pleural wall or in contact with mesothelial cells at any time.
  • Long fibers produced fibrosis: the ratio of hydroxyproline (a collagen measure) to total protein rose above control values by 2 weeks. Short fibers produced no difference from controls.
  • In the long-fiber group, no plaques and no mesotheliomas were found at 16 weeks.
• The authors' conclusion: The authors concluded that mesothelial and subpleural cell proliferation occurs in response to long crocidolite fibers. They suggested this results from cytokine secretion by interstitial macrophages responding to the fibers, without fibers needing to reach the pleura. They speculated that repeated or prolonged activation may be involved in subpleural fibrosis or mesotheliomas.
• Limitations the authors state:
  • The authors said the absence of extensive pleural fibrosis or mesotheliomas may be related to the single exposure, the dose level, or the limited observation period.
  • The authors noted that histological examination is not the ideal method for locating fibers.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Deposition, Pleura, Crocidolite, Fibrosis, Alveoli, Interstitial, Epithelium.

Related studies

• Mesothelial cell proliferation: a nonspecific response to lung injury associated with fibrosis — I.Y. Adamson, J. Bakowska, et al. (1994)
• Response of mouse lung to crocidolite asbestos. 1. Minimal fibrotic reaction to short fibres — I.Y. Adamson, D.H. Bowden (1987)
• Response of mouse lung to crocidolite asbestos. 2. Pulmonary fibrosis after long fibres — I.Y. Adamson, D.H. Bowden (1987)
• Strain differences in pleural mesothelial cell reactions induced by potassium octatitanate fibers (TISMO) infused directly into the thoracic cavity — M. Yokohira, Y. Nakano, et al. (2013)
• Long and short fiber amosite asbestos alters at a different extent the redox metabolism in human lung epithelial cells — C. Riganti, E. Aldieri, et al. (2003)
• 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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