Early mesothelial cell proliferation after asbestos exposure: in vivo and in vitro studies

Our plain-English summary of Early mesothelial cell proliferation after asbestos exposure: in vivo and in vitro studies, by I.Y. Adamson (Environmental Health Perspectives, 1997).

The study

• Author: I.Y. Adamson
• Journal: Environmental Health Perspectives
• Published: 1997;105 Suppl 5(Suppl 5):1205-8
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

There is some evidence that proliferation of pleural mesothelial cells (MC) occurs soon after deposition of asbestos fibers. To study this effect, we instilled a single dose of 0.1 mg crocidolite into the lungs of mice for 1 and 6 weeks and counted labeled nuclei after 3H-thymidine (3HT) injection. Short fibers (< 1 micron) induced little change in the lung; they were mostly phagocytized and had a minimal effect on MC labeling. Long fibers up to 20 microns damaged the bronchiolar epithelium and were incorporated into connective tissue. Increased 3HT uptake was seen in fibroblasts and epithelial cells and also in MC, which peaked at 2% labeled at 1 week compared to near 0% labeling in controls. No fibers were found in or near labeled MC, which suggested that a cytokine generated in the lung during the early response phase might induce MC proliferation. To look for a cytokine effect in vitro, we instilled asbestos into rat lungs and, after 1 and 6 weeks, bronchoalveolar and pleural lavage fluids as well as macrophages were collected. Alveolar macrophages contained fibers, but pleural macrophages (PM) did not. After short-term culture, macrophage supernatants and the lavage fluids were tested on rat lung MC in culture. At 1 week, PM secreted growth factor(s) for MC, and the mitogenic effect was more pronounced with lavage fluids. No effects on MC were found using material prepared 6 weeks after asbestos. The early MC growth increase was not blocked by antibodies to cytokines, such as platelet-derived growth factor, fibroblast growth factors, or tumor necrosis factor, but was inhibited by anti-keratinocyte growth factor (anti-KGF). The results show that an early growth phase of MC after asbestos exposure appears unrelated to particle translocation to the pleura but is associated with cytokine release, most likely KGF, by lung cells.

In plain English

In this animal and laboratory study, the author asked whether asbestos fibers must reach the pleura (the lung lining) to make mesothelial cells there divide. Mice received 0.1 mg of long or short crocidolite fibers into the lungs, and dividing cells were counted with a radioactive label for up to 6 weeks. After long fibers, labeled mesothelial cells peaked at more than 2% at 1 week, versus near zero in controls, and returned to normal by 4 weeks. Short fibers caused only a brief small rise at 3 days. In rats given crocidolite, 58.3% of air-space macrophages held fibers at 1 week, but no pleural macrophages did. Pleural fluid from 1-week rats nearly doubled label uptake by cultured rat mesothelial cells, while 6-week samples had no effect. An antibody to keratinocyte growth factor (KGF) blocked this effect. The author concluded that early mesothelial growth appeared unrelated to fibers reaching the pleura and was associated with a substance released by lung cells, most likely KGF. The study measured cell division, not mesothelioma.

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 (mice and rats given asbestos into the lungs) combined with in vitro (cell culture) tests on rat lung mesothelial cells
• Who was studied: Swiss Webster mice, killed in groups of four at times up to 6 weeks after exposure. 150-g male rats, killed in groups of six at 1 and 6 weeks. Rat lung mesothelial cells from the American Type Culture Collection were used for the culture tests. Department of Pathology, University of Manitoba, Winnipeg, Canada.
• Exposure: A standard UICC crocidolite sample, separated into long fibers (mean length 24.4 micrometres plus or minus 0.5, with 88% longer than 2.5 micrometres) and short fibers (0.6 micrometres plus or minus 0.1). Mice received 0.1 mg of either preparation instilled into the trachea. Rats received 0.5 mg of mixed-length UICC crocidolite injected into the trachea. Controls received water only.
• Main results:
  • Mice given long fibers: labeled (dividing) lung cells reached 3% of all cells at 1 week.
  • Mice given long fibers: labeled mesothelial cells peaked at more than 2% at 1 week and did not return to normal until 4 weeks.
  • Mice given short fibers: mesothelial cell labeling showed only a brief small increase at 3 days. At other times it was at the control level of near zero.
  • Mice given short fibers: little change in lung structure and no fibrosis, by microscopy or by chemical measurement.
  • Mice given long fibers: the areas around the small airways became more fibrotic over time, and fibrosis was confirmed chemically.
  • Rats: fibers were found in 58.3% of alveolar macrophages at 1 week and 28.5% at 6 weeks. None of the pleural macrophages contained asbestos by light microscopy.
  • Rats: electron microscopy also found no fibers in pleural macrophages.
  • Rats: mesothelial cell labeling was increased at 1 week but not at 6 weeks. The article states these data were not shown.
  • Cell culture: samples from control animals did not affect label uptake by mesothelial cells.
  • Cell culture, samples taken 1 week after asbestos: pleural macrophage supernatant at 25% of volume increased mesothelial cell growth by about 40%. The two concentrations of alveolar macrophage supernatant had little effect.
  • Cell culture, samples taken 1 week after asbestos: pleural lavage fluid almost doubled label uptake by mesothelial cells.
  • Cell culture: lavage fluids and macrophage supernatants taken 6 weeks after asbestos had no effect on mesothelial cell label uptake.
  • Antibodies to PDGF, FGFa, FGFb, TGF-beta and TNF-alpha did not reduce the increased mesothelial cell DNA synthesis caused by 1-week pleural lavage fluid.
  • Antibodies to EGF and TGF-alpha produced only a small (15%) inhibition. The article states these data were not shown.
  • Antibody to keratinocyte growth factor (anti-KGF) gave the greatest inhibition and blocked the growth-promoting effect of pleural lavage fluid.
  • Pure recombinant KGF added to normal resting rat mesothelial cells increased label uptake at 1 day.
• The authors' conclusion: The author concluded that an early growth phase of mesothelial cells after asbestos exposure appears unrelated to fibers moving to the pleura. It is instead associated with cytokine release by lung cells, most likely KGF. The author also suggested that repeated exposures may cause prolonged mesothelial proliferation without asbestos fibers acting directly on pleural cells.

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, Asbestos Exposure, Deposition, Crocidolite, Epithelium, Fibroblast, Cytokine, Macrophage.

Related studies

• Novel cell imaging techniques show induction of apoptosis and proliferation in mesothelial cells by asbestos — J.L. Goldberg, C.L. Zanella, et al. (1997)
• 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: a nonspecific response to lung injury associated with fibrosis — I.Y. Adamson, J. Bakowska, et al. (1994)
• Patterns of 8-hydroxydeoxyguanosine formation in DNA and indications of oxidative stress in rat and human pleural mesothelial cells after exposure to crocidolite asbestos — H. Fung, Y.W. Kow, et al. (1997)
• Role of fibre characteristics on cytotoxicity and induction of anaphase/telophase aberrations in rat pleural mesothelial cells in vitro: correlations with in vivo animal findings — M. Yegles, X. Janson, et al. (1995)
• KGF and HGF are growth factors for mesothelial cells in pleural lavage fluid after intratracheal asbestos — I.Y. Adamson, J. Bakowska (2001)

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