Chrysotile asbestos induces PDGF-A chain-dependent proliferation in human and rat lung fibroblasts in vitro

Our plain-English summary of Chrysotile asbestos induces PDGF-A chain-dependent proliferation in human and rat lung fibroblasts in vitro, by J.A. Lasky, J.C. Bonner, B. Tonthat, et al (Chest, 1996).

The study

• Authors: J.A. Lasky, J.C. Bonner, B. Tonthat, A.R. Brody
• Journal: Chest
• Published: 1996;109(3 Suppl):26S-28S
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

This conference report asked whether chrysotile asbestos fibers can directly stimulate the growth of lung fibroblasts in the absence of other cell types and outside factors, and whether human lung fibroblasts respond as rat lung fibroblasts did in the authors' earlier work. Primary human lung fibroblasts were isolated from normal lung tissue removed during lobectomy or pneumonectomy for lung cancer. Cells from two donors were characterized by immunostaining. The isolates stained for vimentin but not for desmin, factor VIII or neurofilament protein. About 10% stained weakly for alpha-smooth muscle actin, so the isolates were judged to be about 90% fibroblasts and 10% myofibroblasts. Northern blot analysis showed that the human cells made PDGF-A chain mRNA. The cells also proliferated in response to recombinant PDGF-AA, which the authors took to show that they express the PDGF-alpha receptor. Quiescent rat and human fibroblasts were exposed for 3 days to sheared, sonicated, sterile chrysotile at 0.05 to 5 µg/cm2, and growth was measured with a colorimetric proliferation assay. Both rat and human fibroblasts proliferated in response to chrysotile. Asbestos was toxic to human fibroblasts at doses above 10 µg/cm2. In preliminary experiments, PDGF-A chain antisense oligomers blocked the asbestos-induced growth of human fibroblasts, while sense-strand controls did not. The authors concluded that asbestos is mitogenic for rat and human lung fibroblasts in vitro through a PDGF-A chain-dependent mechanism.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This short conference paper reported laboratory experiments on lung cells grown in dishes. No people or animals were exposed. The authors isolated fibroblasts (connective-tissue cells) from two human donors, using normal lung tissue removed during lung cancer surgery, and also used rat lung fibroblasts. The human isolates were about 90% fibroblasts and 10% myofibroblasts. The human cells made the genetic message for a growth factor called PDGF-A chain and multiplied when given PDGF-AA, so the authors concluded that they carry its receptor. Resting human and rat cells exposed for 3 days to sterile chrysotile asbestos fibers at 0.05 to 5 micrograms per square centimetre both multiplied. Asbestos was toxic to the human cells at doses above 10 micrograms per square centimetre. In what the authors called preliminary experiments, PDGF-A chain antisense molecules stopped the asbestos-induced growth of the human cells, while control molecules did not. The authors concluded that asbestos stimulates rat and human lung fibroblast growth in vitro through a PDGF-A chain-dependent mechanism. They noted that it is not known whether this happens in living lungs.

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: Laboratory (in vitro) experiment on cultured rat lung fibroblasts and human lung fibroblasts from two donors; short conference paper
• Who was studied: Primary human lung fibroblasts isolated from normal lung tissue removed during surgery for lung cancer (lobectomy or pneumonectomy), taken from a part of the lobe away from the cancerous nodule, together with rat lung fibroblasts
• Exposure: Sheared and sonicated sterile chrysotile asbestos fibers at 0.05 to 5 micrograms per square centimetre, applied to resting (quiescent) cells for 3 days
• Main results:
  • Staining showed that the human lung cell isolates were about 90% fibroblasts and 10% myofibroblasts
  • The human lung fibroblasts made PDGF-A chain messenger RNA
  • The human fibroblasts multiplied in response to PDGF-AA, from which the authors concluded that they express the PDGF-alpha receptor
  • Rat lung fibroblasts increased in number after chrysotile exposure, at doses and to a degree similar to the authors' earlier published results
  • Resting human lung fibroblasts also multiplied after chrysotile exposure. The figure marks some doses as p less than 0.05, with results pooled from three experiments for rat cells and six for human cells
  • Asbestos was toxic to the human fibroblasts at doses above 10 micrograms per square centimetre (data not shown)
  • In preliminary experiments, PDGF-A chain antisense molecules blocked the asbestos-induced growth of the human fibroblasts. The article does not report measuring whether these molecules reduced PDGF-A chain production
  • The control (sense-strand) molecules did not inhibit cell growth
• The authors' conclusion: The authors concluded that asbestos is mitogenic (growth-stimulating) for both rat and human lung fibroblasts in vitro through a PDGF-A chain-dependent mechanism
• Limitations the authors state:
  • The antisense experiments were described as preliminary
  • It is not known whether this PDGF-A chain-dependent growth mechanism operates in living lungs with asbestos-induced fibrosis

Topics

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

Medical terms in this study, explained in our Lexicon: Chrysotile, Platelet-Derived Growth Factor (PDGF), Fibroblast, Pneumonectomy, Lung Cancer, Desmin.

Related studies

• Chrysotile asbestos upregulates gene expression and production of alpha-receptors for platelet-derived growth factor (PDGF-AA) on rat lung fibroblasts — J.C. Bonner, A.L. Goodell, et al. (1993)
• Chrysotile asbestos stimulates platelet-derived growth factor-AA production by rat lung fibroblasts in vitro: evidence for an autocrine loop — J.A. Lasky, P.G. Coin, et al. (1995)
• Differential proliferation of rat lung fibroblasts induced by the platelet-derived growth factor-AA, -AB, and -BB isoforms secreted by rat alveolar macrophages — J.C. Bonner, A.R. Osornio-Vargas, et al. (1991)
• Rat alveolar macrophage-derived platelet-derived growth factor is chemotactic for rat lung fibroblasts — A.R. Osornio-Vargas, J.C. Bonner, et al. (1990)
• Primary lung fibroblasts from the 129 mouse strain exhibit reduced growth factor responsiveness in vitro — D.M. Brass, S.Y. Tsai, et al. (2001)
• Morphological transformation in vitro of normal human fibroblasts by chrysotile — L.B. Joseph, R.E. Stephens, et al. (1983)

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