The pathobiology of asbestos-induced lung disease: a proposed role for macrophage-derived growth factors

Our plain-English summary of The pathobiology of asbestos-induced lung disease: a proposed role for macrophage-derived growth factors, by J.A. Lasky, J.C. Bonner, A.R. Brody (Annals of the New York Academy of Sciences, 1991).

The study

• Authors: J.A. Lasky, J.C. Bonner, A.R. Brody
• Journal: Annals of the New York Academy of Sciences
• Published: 1991;643:239-44
• Type of article: Review
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

In plain English

This article reviewed the authors' laboratory's earlier rat experiments on early changes behind asbestos-related lung scarring (fibrosis) after one brief, intense exposure. It reported no new study. Rats breathed chrysotile or crocidolite asbestos for a few hours. Both fiber types landed mainly where small air ducts deep in the lung branch. One study found that 19% of breathable crocidolite and 23% of chrysotile was deposited, by mass. A month later, 25% of the deposited crocidolite and 19% of the chrysotile remained. Thirty days after chrysotile exposure, rats previously exposed to ozone retained twice as many fibers as rats without ozone. Scavenger cells (macrophages) gathered at the fiber sites within hours, partly through a blood protein system called complement. After chrysotile exposure, more cells took up tritiated thymidine, a marker of cell proliferation, especially at those sites. In rats exposed to iron spheres or room air, under 1% of cells took it up. Macrophages released a growth factor resembling platelet-derived growth factor (PDGF), which stimulates lung fibroblasts. The authors proposed that such growth factors help drive fibrosis and called for much more research.

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: Review of the authors' own laboratory's previously published animal experiments (rats, and mice in one set of studies); no new data
• Who was studied: Laboratory rats (8- to 10-week-old CD rats in the deposition experiments) and, in one set of complement experiments, C5a-deficient mice. Rat alveolar macrophages were also studied in culture. Animal numbers are not given in this review.
• Exposure: Single brief exposures to airborne chrysotile or crocidolite asbestos in open chambers. Exposures lasted 1 to 3 hours in the deposition studies. In the cell-proliferation studies, chrysotile at 10 mg/m3 respirable mass for 5 hours was compared with iron spheres at 33 mg/m3 and with room air. Some rats were exposed to ozone before chrysotile.
• Main results:
  • In the reviewed rat studies, inhaled fibers were deposited mainly on alveolar duct bifurcations, most of all on the first bifurcation. Very few fibers were deposited elsewhere.
  • Roggli and Brody, as reported in the review, found deposition of 19% of respirable crocidolite fibers and 23% of chrysotile, by mass.
  • In rats killed one month after a single exposure, 25% of the deposited crocidolite and 19% of the deposited chrysotile was retained, by mass.
  • Thirty days after chrysotile exposure, rats previously exposed to ozone retained twice as many fibers as the control group. Initial deposition did not differ between the two groups.
  • Complement was partly responsible for macrophages gathering at the fiber sites. C5a-deficient mice had fewer macrophages at alveolar duct bifurcations 48 hours after asbestos exposure than exposed mice with normal C5 levels. The review notes the response was blunted but still elevated, so it was not entirely complement-mediated.
  • Rats exposed to iron spheres or room air always had fewer than 1% of cells incorporating tritiated thymidine, a marker used to assess cell proliferation. Chrysotile-exposed rats showed significantly increased thymidine incorporation in several lung cell types 33 hours after exposure.
  • In chrysotile-exposed rats, thymidine labeling of epithelial cells rose further down the airways: tracheal epithelium 0.59%, bronchial epithelium 1.09% (printed 'I .09%' in the scanned text), large airways 2.44%, and lower lung 5.42%.
  • Chang et al., as reported in the review, found a 78% increase in the volume of the alveolar duct bifurcation epithelium after 1 hour of chrysotile exposure. The article prints the time of measurement as '2 hours post exposure'. There was no statistically significant increase at 30 days.
  • The interstitium (the tissue around the bifurcation) increased in volume by 28% at 2 days and by 67% at 30 days after exposure.
  • Rat alveolar macrophages secreted a PDGF homologue. In macrophage-conditioned medium, about 50% of it was bound to a protein larger than 200,000 daltons (an alpha-macroglobulin), 30% was bound to a protein of about 150,000 daltons, and 20% was unbound.
• The authors' conclusion: The authors concluded that, in this rat model, a single brief exposure to respirable asbestos produces proliferative lesions where most fibers deposit. They proposed that macrophages, drawn to the fibers partly by complement, secrete PDGF, which attracts and stimulates rat lung fibroblasts. They added that other cytokines, such as TGF-beta and TNF, are likely also involved.
• Limitations the authors state:
  • The authors stated that much further research is needed to determine how much each cytokine contributes to the fibrogenic response and how the cytokines are regulated.
  • The authors stated that the biological significance of PDGF binding to alpha-macroglobulins was unknown.

Topics

Medical terms in this study, explained in our Lexicon: Macrophage.

Related studies

• 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)
• 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)
• Growth factor responses and protooncogene expression of murine mesothelial cell lines derived from asbestos-induced mesotheliomas — L.A. Goodglick, C.A. Vaslet, et al. (1997)
• Monocyte-derived growth factors in asbestos-induced interstitial fibrosis — D.A. Schwartz, L. Rosenstock, et al. (1989)
• Distinctive profile of alveolar macrophage-derived cytokine release induced by fibrogenic and nonfibrogenic mineral dusts — I. Lemaire, S. Ouellet (1996)
• Relative release of interleukin-1 beta and interleukin-1 receptor antagonist by alveolar macrophages. A study in asbestos-induced lung disease, sarcoidosis, and idiopathic pulmonary fibrosis — J.N. Kline, D.A. Schwartz, et al. (1993)

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