Fibronectin and procollagen 3 levels in bronchoalveolar lavage of asbestos-exposed human subjects and sheep

Our plain-English summary of Fibronectin and procollagen 3 levels in bronchoalveolar lavage of asbestos-exposed human subjects and sheep, by R. Bégin, M. Martel, Y. Desmarais, et al (Chest, 1986).

The study

• Authors: R. Bégin, M. Martel, Y. Desmarais, G. Drapeau, R. Boileau, M. Rola-Pleszczynski, S. Massé
• Journal: Chest
• Published: 1986;89(2):237-43
• Cited by: 66 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

To evaluate the potential interest of levels of fibronectin and procollagen 3 in bronchoalveolar lavage fluid as markers of fibrogenic activity, we characterized the time course of changes in fibronectin and procollagen 3 levels in the tracheal lobe of sheep exposed to nonfibrogenic and fibrogenic materials. We correlated these observations with those of bronchoalveolar lavage in long-term asbestos workers in various stages of disease activity. Following studies before exposure, the tracheal lobe of three groups of 24 sheep were exposed once to 100 ml of phosphate-buffered saline solution (PBS), to 100 mg of latex beads in 100 ml of PBS, or to 100 mg of chrysotile fibers in 100 ml of PBS. Bronchoalveolar lavages were obtained at 0, 1, 2, 4, 8, and 12 months after exposure, and four or five sheep per group were killed after each lavage for histopathologic analysis. Fibronectin in bronchoalveolar lavage fluid increased significantly only in the asbestos-exposed sheep to values two to three times above controls or latex-exposed sheep and remained elevated during the 12 months of the study. Levels of procollagen 3 in bronchoalveolar lavage fluid were increased significantly only during the first two months following exposure in the asbestos-exposed sheep only. In the asbestos workers without disease, levels of fibronectin and procollagen 3 in bronchoalveolar lavage fluid were comparable to controls, but these levels were significantly elevated in those with asbestos-associated alveolitis or asbestosis. This study documents that the measurement of levels of fibronectin and procollagen 3 in bronchoalveolar lavage fluid assesses fibrogenic activity of alveolitis and should be useful to predict its progression in a fibrotic process. In asbestos workers the potential use of these markers is primarily related to early detection of asbestos-induced pulmonary injury.

In plain English

This study combined a sheep experiment with lung-wash tests in asbestos workers. Sheep in three groups of 24 had one lung lobe given a single dose of salt solution, 100 mg of latex beads, or 100 mg of UICC Canadian chrysotile. The lobe was then washed (bronchoalveolar lavage) over 12 months. Fibronectin rose significantly only in the chrysotile-exposed sheep and kept rising. Procollagen 3 rose early and was back to control levels by month 4. Chrysotile-exposed lobes developed small-airway scarring (fibrosis); latex-exposed lobes returned to normal. The human part compared 34 asbestos workers, exposed only to Canadian chrysotile in Quebec mines and mills, with unexposed control workers. Workers without lung damage had levels similar to controls. In workers with asbestosis, both markers were significantly higher than in controls. Workers with alveolitis (lung inflammation) but not asbestosis had a significantly higher procollagen 3 to albumin ratio. Their fibronectin to albumin ratio was reported as not significant, though the Discussion calls their fibronectin significantly higher than in undamaged exposed workers. The authors concluded these markers assess fibrogenic activity and should be useful to predict progression to fibrosis.

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 in sheep (saline, latex and chrysotile groups followed over 12 months), combined with a comparison of bronchoalveolar lavage findings in asbestos workers at different disease stages and unexposed control workers
• Who was studied: 72 male sheep in three groups of 24. Also 34 asbestos workers aged 42 to 70, divided into 7 without asbestos-induced lung damage, 8 with alveolitis but not meeting criteria for asbestosis, and 19 with asbestosis, compared with 21 manual workers without asbestos exposure.
• Exposure: Sheep: a single dose of 100 mg of UICC Canadian chrysotile, or 100 mg of latex beads, or saline, put into one lung lobe. Workers: Canadian chrysotile only, in the mines and mills of the eastern townships of Quebec, for an average of 33 ± 5 years (range 24 to 42).
• Main results:
  • In sheep, fibronectin in lavage fluid was significantly raised only in the chrysotile-exposed group, and levels increased throughout the 12 months.
  • In chrysotile-exposed sheep, procollagen 3 in lavage fluid rose significantly early and returned to control levels at month 4.
  • One year after exposure, in chrysotile-exposed sheep, total cells and macrophages in lavage fluid were still at 150 percent of controls.
  • In chrysotile-exposed sheep at month 12, lesions of the small airways had not regressed and had become fibrotic. Latex-exposed lobes had returned to normal after month 4.
  • In unexposed control workers, the fibronectin to albumin ratio in lavage fluid was 33.7 ± 6.4 micrograms per milligram (results given as mean ± standard error).
  • In asbestos workers without lung damage (group A), the fibronectin to albumin ratio was 33.1 ± 6.0 micrograms per milligram and the procollagen 3 to albumin ratio was 1.03 ± 0.24 ng/mg.
  • In workers with alveolitis but not asbestosis (group B), the fibronectin to albumin ratio was 45.7 ± 34 micrograms per milligram (not significant). The procollagen 3 to albumin ratio was 2.3 ± 0.8 ng/mg (p less than 0.05 versus controls and group A).
  • In the Discussion, the authors state that group B had significantly higher levels of total cells, macrophages, neutrophils, fibronectin and procollagen 3 in lavage fluid than exposed workers with a normal gallium scan and pressure-volume curve (group A).
  • In workers with asbestosis (group C), the fibronectin to albumin ratio was 71.4 ± 32 micrograms per milligram, significantly higher than controls and group A. The procollagen 3 to albumin ratio was 2.0 ± 0.8 ng/mg (p less than 0.05 versus controls and group A).
  • Excluding smokers did not significantly change the human results.
• The authors' conclusion: The authors concluded that measuring fibronectin and procollagen 3 in lavage fluid assesses the fibrogenic (scar-forming) activity of alveolitis and should be useful to predict its progression to fibrosis. In their closing section they wrote that it "can predict" this progression.

Topics

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

Medical terms in this study, explained in our Lexicon: Bronchoalveolar Lavage (BAL), Fibrogenic, Chrysotile.

Related studies

• Assessment of progression of asbestosis in the sheep model by bronchoalveolar lavage and pulmonary function tests — R. Bégin, M. Rola-Pleszczynski, et al. (1983)
• Biochemical components of bronchoalveolar lavage in early experimental asbestosis of the sheep: phospholipase A2 activity, prostaglandin E2 and proteins — P. Sirois, G. Drapeau, et al. (1983)
• Pulmonary and pleural leukocytes from F344 rats produce elevated levels of fibronectin following inhalation of refractory ceramic fibers — T.R. Gelzleichter, J.B. Mangum, et al. (1996)
• Pulmonary uptake of gallium-67 in asbestos-exposed humans and sheep — R. Bégin, A. Cantin, et al. (1983)
• Peroxisome proliferator-activated receptor-gamma ligands suppress fibronectin gene expression in human lung carcinoma cells: involvement of both CRE and Sp1 — S. Han, J.D. Ritzenthaler, et al. (2005)
• Tenascin and fibronectin expression in human mesothelial cells and pleural mesothelioma cell-line cells — V.L. Kinnula, A. Linnala, et al. (1998)

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