Mesothelial cell proliferation: a nonspecific response to lung injury associated with fibrosis

Our plain-English summary of Mesothelial cell proliferation: a nonspecific response to lung injury associated with fibrosis, by I.Y. Adamson, J. Bakowska, D.H. Bowden (American Journal of Respiratory Cell and Molecular Biology, 1994).

The study

• Authors: I.Y. Adamson, J. Bakowska, D.H. Bowden
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1994;10(3):253-8
• Cited by: 36 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

An early proliferative response of mesothelial and subpleural cells has been reported in animals after inhalation or intratracheal (I.T.) instillation to the lung of long asbestos fibers, which also induce pulmonary fibrosis. To determine whether this cell proliferation is directly related to asbestos exposure or is a nonspecific response to injury, we examined [3H]thymidine (3HT) uptake by cells at the pleura after exposing mice to 5 days of hyperoxia, to intravenous (I.V.) (3 mg) or I.T. (0.15 mg) bleomycin, to I.T. (1 mg) silica, and to I.T. (0.1 mg) crocidolite asbestos of mixed length. All exposures induced acute lung injury, as shown by high levels of protein in lavage fluid. After hyperoxia, the percentage of total lung cells labeled by 3HT in autoradiographs was high for only a few days, as repair took place with no increase in fibroblast growth and no subsequent development of fibrosis. Particle or bleomycin exposure induced a prolonged increase in 3HT uptake with enhanced fibroblast labeling over a 4- to 6-wk period. In each case, labeled subpleural cells, mainly fibroblasts, increased up to 10-fold in the first 2 to 4 wk. At the same time, 3HT uptake by mesothelial cells ranged from 1.4 to 3% compared with almost zero in controls and in oxygen-exposed mice after a few days upon return to air. These results indicate that mesothelial and subpleural cell proliferation occurs after various types of injury to the lung. The close temporal association between 3HT uptake by mesothelial cells and fibroblasts during the reparative phase suggests that mesothelial cells may respond to the same cytokines that trigger interstitial fibrosis.

In plain English

This was an experiment in mice. The authors re-examined lung tissue from earlier experiments to count dividing cells, using a radioactive marker that is taken up by cells copying their DNA. Earlier work had found more dividing cells in the lung lining (mesothelial cells) and in the cells just beneath it (subpleural cells) after long asbestos fibers. The authors asked whether this response was specific to asbestos. Male Swiss Webster mice received one of several treatments: crocidolite asbestos of mixed fiber length (0.1 mg) or silica (1 mg) placed into the windpipe; the drug bleomycin given into the windpipe or a vein; or 90% oxygen for 5 days. Saline-treated mice were controls. All treatments injured the lungs. Asbestos, silica and bleomycin raised lung collagen to about twice control levels, but oxygen did not. In controls, 0 to 0.1% of mesothelial cells were dividing. Up to 3% were dividing within 1 week after mixed-length asbestos, and about 1.5% at 1 week after bleomycin. After oxygen, about 1% were dividing at 3 days, falling to near zero by day 5. The authors concluded that the mesothelial response is nonspecific and is prolonged only when fibrosis develops.

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 in mice. It was a retrospective analysis of tissue from experiments whose full details had been published before, now with detailed cell-labeling counts added.
• Who was studied: 25-g male Swiss Webster mice, killed in groups of four at time intervals after treatment. The work was done at the Department of Pathology, University of Manitoba, Winnipeg, Canada. The total number of mice and the study dates are not given.
• Exposure: Five treatments were compared:
• 0.1 mg of a mixed-length crocidolite asbestos sample (DICC), placed into the windpipe
• 1 mg silica (quartz), placed into the windpipe
• 0.15 mg bleomycin, placed into the windpipe
• 3 mg bleomycin, injected into a vein
• 90% oxygen for 5 days
  Saline-injected mice were the controls.
• Main results:
  • In all treated groups, the highest protein level in lung-wash (lavage) fluid, a measure of lung injury, was significantly higher than in controls.
  • Lung collagen did not increase after oxygen exposure. After bleomycin (either route), silica and crocidolite asbestos it was significantly increased from 4 weeks onward, with maximal values at about twice control levels.
  • After bleomycin, silica or asbestos, uptake of the marker by all lung cells rose sharply to 8 to 10 times control values. From 2 to 8 weeks, most of the labeled cells were fibroblasts.
  • In control mice, about 0.3% of subpleural cells and only 0 to 0.1% of mesothelial cells were labeled.
  • After oxygen exposure, about 1% of mesothelial cells were labeled at 3 days, falling to near zero by day 5.
  • After silica or asbestos, mesothelial cell labeling peaked within 1 week, with up to 3% labeled in response to mixed-length asbestos. It was back at control levels by 4 weeks.
  • After bleomycin, mesothelial cell labeling peaked at 1 week, when about 1.5% of cells were labeled, compared with zero in controls.
  • The authors did not observe silica or asbestos moving directly to the pleural surface.
• The authors' conclusion: The authors concluded that mesothelial cell proliferation is a nonspecific response that occurs in the acute phase after several types of lung injury, and that it is prolonged only when fibrosis develops. They suggested that mesothelial cells may respond to cytokines (chemical signals) released by activated interstitial macrophages.
• Limitations the authors state:
  • The authors could not identify any specific cytokine with the material available for this retrospective study.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Fibrosis, Pulmonary Fibrosis, Asbestos Exposure, Pleura, Crocidolite, Fibroblast, Cytokine.

Related studies

• Lung mesothelial cell and fibroblast responses to pleural and alveolar macrophage supernatants and to lavage fluids from crocidolite-exposed rats — I.Y. Adamson, H. Prieditis, et al. (1997)
• Mesothelial cell proliferation after instillation of long or short asbestos fibers into mouse lung — I.Y. Adamson, J. Bakowska, et al. (1993)
• Early mesothelial cell proliferation after asbestos exposure: in vivo and in vitro studies — I.Y. Adamson (1997)
• Response of mouse lung to crocidolite asbestos. 2. Pulmonary fibrosis after long fibres — I.Y. Adamson, D.H. Bowden (1987)
• Novel cell imaging techniques show induction of apoptosis and proliferation in mesothelial cells by asbestos — J.L. Goldberg, C.L. Zanella, et al. (1997)
• Proliferation of rat pleural mesothelial cells in response to hepatocyte and keratinocyte growth factors — I.Y. Adamson, J. Bakowska, et al. (2000)

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