KGF and HGF are growth factors for mesothelial cells in pleural lavage fluid after intratracheal asbestos

Our plain-English summary of KGF and HGF are growth factors for mesothelial cells in pleural lavage fluid after intratracheal asbestos, by I.Y. Adamson, J. Bakowska (Experimental Lung Research, 2001).

The study

• Authors: I.Y. Adamson, J. Bakowska
• Journal: Experimental Lung Research
• Published: 2001;27(7):605-16
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mesothelial cells proliferate soon after asbestos deposition in the lung. The present study investigates whether the known mesothelial cell mitogens keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) are present in the lung and specifically in the pleural cavity during the phase of mesothelial cell growth. Rats received 1 mg crocidolite asbestos in 0.5 mL water by intratracheal instillation and were killed up to 2 weeks later; tritiated thymidine was injected 1 hour before death. Bronchoalveolar lavage (BAL) and pleural lavage (PLL) were performed. Increased inflammatory cell numbers and protein levels were found in BAL but also in PLL at 1 day after asbestos deposition. In lung sections, labeling of mesothelial cells increased > 10-fold at day 1 and stayed above normal for 1 week. During this period, the levels of HGF and KGF were significantly raised in both BAL and PLL fluids. The PLL fluid had mitogenic activity for mesothelial cells in culture and this effect was significantly reduced by antibodies to HGF and KGF. The results indicate that fiber deposition in the airspaces rapidly induces lung injury and inflammation, in which growth factors for mesothelial cells KGF and HGF are secreted. These factors reach the pleural cavity at the time when mesothelial cell proliferation occurs. It is possible that the activated, dividing mesothelial population may then be more susceptible to DNA damage by any translocated fibers.

In plain English

In this animal experiment, the authors put 1 mg of UICC crocidolite asbestos in water into the windpipes of 20 male Sprague-Dawley rats; controls received water only. Groups of 4 were killed at days 0, 1, 3, 7 and 14. Fluid was washed out of the lungs (bronchoalveolar lavage) and the chest cavity around them (pleural lavage). After asbestos, pleural fluid held more cells than normal at day 1. Two growth factors, HGF and KGF, were significantly raised in both fluids at days 1 and 3. The share of mesothelial cells (lining the lung surface) labeled by tritiated thymidine, a marker of DNA synthesis, rose from 0.1% in controls to about 1.5% at day 1, staying above normal at 1 week. In lab dishes, pleural fluid taken 3 days after asbestos almost doubled mesothelial cells' thymidine uptake over 24 hours. Antibodies against both factors together reduced this effect most, but not fully to control levels. The authors concluded these factors are likely responsible for the early increase in mesothelial cell proliferation. They noted that only a single dose was tested.

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 (rats given asbestos into the windpipe, compared with water-injected controls), with a follow-up cell culture experiment
• Who was studied: 20 male Sprague-Dawley rats (about 250 g) given asbestos, killed in groups of 4 at days 0, 1, 3, 7 and 14; water-injected control rats; rat lung mesothelial cells in culture. The authors are from the Department of Pathology, University of Manitoba, Winnipeg, Canada; study dates are not given.
• Exposure: a single dose of 1 mg UICC crocidolite asbestos in 0.5 mL water, injected into the windpipe (intratracheal instillation)
• Main results:
  • In asbestos-treated rats, the number of cells recovered by pleural lavage was greater than normal at 1 day.
  • In asbestos-treated rats, the protein level in BAL fluid increased 4-fold at day 1 and did not return to normal for more than 1 week.
  • HGF in BAL fluid was around 16 pg/mL in controls and increased 3-fold at days 1 and 3 after asbestos, returning to the normal range by day 7.
  • KGF in controls was around 6 pg/mL in BAL and 4 pg/mL in pleural lavage fluid. After asbestos it was significantly increased at days 1 and 3 in both fluids.
  • The percentage of mesothelial cells labeled by tritiated thymidine (a marker of DNA synthesis) was 0.1% in controls and about 1.5% at day 1 after asbestos. It was still above normal at 1 week.
  • In culture, pleural lavage fluid from rats 3 days after asbestos almost doubled mesothelial cells' uptake of tritiated thymidine over 24 hours, a measure the authors used to assess proliferation.
  • Antibodies to both HGF and KGF together gave the greatest reduction of this effect, but thymidine uptake did not fall completely to control values.
• The authors' conclusion: The authors concluded that KGF and HGF are likely to be responsible for the increased mesothelial cell proliferation seen soon after asbestos deposition in the lung. They suggested that activated, dividing mesothelial cells may be more susceptible to DNA damage by fibers that move to the pleura.
• Limitations the authors state:
  • The experiments examined only a single dose of asbestos; the authors' comments on repeated exposure are a projection.
  • Because blocking KGF and HGF did not bring thymidine uptake fully back to control levels, other factors may also play a role.
  • The growth factor test kits were designed for human growth factors, not rat. The authors state they had previously validated them for rat lavage fluid.

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, Deposition, Pleural Cavity, Crocidolite, Bronchoalveolar Lavage (BAL), Inflammation.

Related studies

• Proliferation of rat pleural mesothelial cells in response to hepatocyte and keratinocyte growth factors — I.Y. Adamson, J. Bakowska, et al. (2000)
• 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)
• Increased expression of epidermal growth factor receptor in rat pleural mesothelial cells correlates with carcinogenicity of mineral fibres — S.P. Faux, C.E. Houghton, et al. (2000)
• 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)
• Expression of growth factor and growth factor receptor RNA in rat pleural mesothelial cells in culture — E. Bermudez, J. Everitt, et al. (1990)
• Early mesothelial cell proliferation after asbestos exposure: in vivo and in vitro studies — I.Y. Adamson (1997)

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