Engraftment of bone marrow progenitor cells in a rat model of asbestos-induced pulmonary fibrosis

Our plain-English summary of Engraftment of bone marrow progenitor cells in a rat model of asbestos-induced pulmonary fibrosis, by J.L. Spees, D.A. Pociask, D.E. Sullivan, et al (American Journal of Respiratory and Critical Care Medicine, 2007).

The study

• Authors: J.L. Spees, D.A. Pociask, D.E. Sullivan, M.J. Whitney, J.A. Lasky, D.J. Prockop, A.R. Brody
• Journal: American Journal of Respiratory and Critical Care Medicine
• Published: 2007;176(4):385-94
• Cited by: 54 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Rationale: Bone marrow-derived cells have been shown to engraft during lung fibrosis. However, it is not known if similar cells engraft consequent to inhalation of asbestos fibers that cause pulmonary fibrosis, or if the cells proliferate and differentiate at sites of injury.

Objectives: We examined whether bone marrow-derived cells participate in the pulmonary fibrosis that is produced by exposure to chrysotile asbestos fibers.

Methods: Adult female rats were lethally irradiated and rescued by bone marrow transplant from male transgenic rats ubiquitously expressing green fluorescent protein (GFP). Three weeks later, the rats were exposed to an asbestos aerosol for 5 hours on three consecutive days. Controls were bone marrow-transplanted but not exposed to asbestos.

Measurements And Main Results: One day and 2.5 weeks after exposure, significant numbers of GFP-labeled male cells had preferentially migrated to the bronchiolar-alveolar duct bifurcations, the specific anatomic site at which asbestos produces the initial fibrogenic lesions. GFP-positive cells were present at the lesions as monocytes and macrophages, fibroblasts, and myofibroblasts or smooth muscle cells. Staining with antibodies to PCNA demonstrated that some of the engrafted cells were proliferating in the lesions and along the bronchioles. Negative results for TUNEL at the lesions confirmed that both PCNA-positive endogenous pulmonary cells and bone marrow-derived cells were proliferating rather than undergoing apoptosis, necrosis, or DNA repair.

Conclusions: Bone marrow-derived cells migrated into developing fibrogenic lesions, differentiated into multiple cell types, and persisted for at least 2.5 weeks after the animals were exposed to aerosolized chrysotile asbestos fibers.

In plain English

This was an animal experiment testing whether cells from the bone marrow take part in lung scarring (fibrosis) caused by chrysotile asbestos. Female rats received a lethal dose of radiation and then a bone marrow transplant from male rats whose cells carry a green fluorescent marker, so the transplanted cells could be traced. Three weeks later the rats breathed chrysotile asbestos fibers (10 mg/m3) for 5 hours a day on three consecutive days. Control rats were transplanted but not exposed. At 1 day and at 2.5 weeks after exposure, significantly more marrow-derived cells were found at the airway branch points where asbestos lesions form than in unexposed controls or in the surrounding lung. These cells became macrophages and connective-tissue cell types, and at 2.5 weeks some made collagen 1. Most of the dividing cells in the lesions were the lung's own cells. The authors found no sign of cell fusion but said that low levels could not be ruled out. They also said it was not yet known whether the cells stay longer than 2.5 weeks.

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 (rat bone marrow transplant model with inhalation exposure to asbestos)
• Who was studied: Female Sprague-Dawley rats given bone marrow from male transgenic rats carrying green fluorescent protein (GFP). Controls were transplanted but not exposed to asbestos. Engraftment was counted in 3 exposed rats at 1 day and 4 exposed rats at 2.5 weeks, with 5 lesions per rat.
• Exposure: Inhaled chrysotile asbestos fibers at 10 mg/m3 for 5 hours on three consecutive days, given three weeks after the bone marrow transplant. Rats were examined 1 day and 2.5 weeks after the last exposure.
• Main results:
  • Total cell number at the first bronchiolar–alveolar duct bifurcations increased significantly after asbestos exposure, compared with transplanted unexposed controls.
  • In asbestos-exposed rats at both 1 day and 2.5 weeks, engraftment of marrow-derived cells at the bronchiolar–alveolar duct regions was highly significant compared with controls.
  • Within the same exposed animals, engraftment was highly significant in the developing lesions compared with the surrounding lung tissue.
  • Marrow-derived cells in the lesions developed into macrophages and mesenchymal (connective-tissue) cell types.
  • At 2.5 weeks after exposure, some marrow-derived cells in the lesions stained for collagen 1, which the authors took as a sign that they were participating in fibrosis.
  • In two animals examined, marrow-derived cells made up less than 0.5% of type II pneumocytes (pro-SP-C positive cells). None were seen inside asbestos lesions.
  • Most of the dividing cells in the lesions came from the lung's own cells, not from bone marrow.
  • Fewer dividing marrow-derived and host cells were seen at 2.5 weeks than at 1 day.
  • No dying (TUNEL-positive) cells were seen in the lesions at either time point.
  • No cells showing signs of cell fusion were found in the lesions examined.
• The authors' conclusion: The authors concluded that bone marrow-derived progenitor cells engraft into asbestos-induced fibrogenic lung lesions and differentiate into macrophages and mesenchymal cell types.
• Limitations the authors state:
  • Low levels of cell fusion could not be entirely excluded by the method used.
  • It was not determined whether the marrow-derived cells persist in the lesions longer than 2.5 weeks.
  • Rare dying cells in the general lung tissue at 2.5 weeks may have been caused by the irradiation rather than by asbestos.
  • It is not known which growth factors, if any, the marrow-derived cells in the lesions produce.

Topics

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

Medical terms in this study, explained in our Lexicon: Pulmonary Fibrosis, Fibrosis, Chrysotile, Fibrogenic, Macrophage, Fibroblast, Apoptosis, Necrosis.

Related studies

• Decreased asbestos-induced lung inflammation and fibrosis after radiation and bone marrow transplant — J. Levis, R. Loi, et al. (2008)
• Changes in autacoid and neuropeptide contents of lung cells in asbestos-induced pulmonary fibrosis — R. Day, S. Lemaire, et al. (1987)
• Upregulation of the PDGF-alpha receptor precedes asbestos-induced lung fibrosis in rats — J.A. Lasky, B. Tonthat, et al. (1998)
• Epithelial-mesenchymal transition involved in pulmonary fibrosis induced by multi-walled carbon nanotubes via TGF-beta/Smad signaling pathway — T. Chen, H. Nie, et al. (2014)
• Alveolar macrophage cytokine and growth factor production in a rat model of crocidolite-induced pulmonary inflammation and fibrosis — K.E. Driscoll, J.K. Maurer, et al. (1995)
• Cytokine regulation of lung fibroblast proliferation. Pulmonary and systemic changes in asbestos-induced pulmonary fibrosis — I. Lemaire, H. Beaudoin, et al. (1986)

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