Increased alveolar plasminogen activator in early asbestosis

Our plain-English summary of Increased alveolar plasminogen activator in early asbestosis, by A. Cantin, C. Allard, R. Bégin (The American Review of Respiratory Disease, 1989).

The study

• Authors: A. Cantin, C. Allard, R. Bégin
• Journal: The American Review of Respiratory Disease
• Published: 1989;139(3):604-9
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Alveolar macrophage-derived plasminogen activator (PA) activity is decreased in some chronic interstitial lung diseases such as idiopathic pulmonary fibrosis and sarcoidosis but increased in experimental models of acute alveolitis. Although asbestos fibers can stimulate alveolar macrophages (AM) to release PA in vitro, the effect of chronic asbestos exposure of the lower respiratory tract on lung PA activity remains unknown. The present study was designed to evaluate PA activity of alveolar macrophages and bronchoalveolar lavage (BAL) fluid in asbestos-exposed sheep and asbestos workers. Forty-three sheep were exposed to either 100 mg UICC chrysotile B asbestos in 100 ml phosphate-buffered saline (PBS) or to 100 ml PBS by tracheal infusion every 2 wk for 18 months. At Month 18, chest roentgenograms were analyzed and alveolar macrophage and extracellular fluid PA activity were measured in samples obtained by BAL. Alveolar macrophage PA activity was increased in the asbestos-exposed sheep compared to control sheep (87.2 +/- 17.3 versus 41.1 +/- 7.2 U/10(5) AM-24 h, p less than 0.05) as was the BAL fluid PA activity (674.9 +/- 168.4 versus 81.3 +/- 19.7 U/mg alb-24 h, p less than 0.01). Among the asbestos-exposed sheep, 10 had normal chest roentgenograms (Group SA) and 15 had irregular interstitial opacities (Group SB). Strikingly, whereas Group SA did not differ from the control group in BAL cellularity or PA activity, Group SB had marked increases in alveolar macrophages (p less than 0.005), AM PA activity (p less than 0.02), and BAL PA activity (p less than 0.001) compared to the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

In plain English

This study measured plasminogen activator (PA), an enzyme from lung immune cells, in lung-washing (lavage) samples from sheep and people. Twenty-five sheep received 100 mg UICC chrysotile B asbestos into the windpipe every 2 weeks for 18 months, and 18 control sheep received salt solution. Exposed sheep had higher PA than controls from macrophages (87.2 ± 17.3 versus 41.1 ± 7.2 units per 10^5 macrophages per 24 hours) and in lavage fluid (674.9 ± 168.4 versus 81.3 ± 19.7 units per milligram of albumin per 24 hours). The rise was statistically significant only in the 15 sheep with abnormal X-rays, not in the 10 with normal X-rays. Among 30 Quebec chrysotile miners and millers, the 13 without disease signs had PA similar to normal subjects. The 7 with early signs (abnormal gallium-67 scans and stiff lungs) had higher levels than normal subjects (477.0 ± 171.0 versus 102.3 ± 10.5, same units). The 10 with definite asbestosis had significantly lower levels than the early-disease group (120.1 ± 20.7). The authors concluded that early asbestos-induced lung inflammation is associated with increased lung PA, and that PA is normal in advanced asbestosis.

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, plus a comparison of lung lavage findings in groups of asbestos workers, normal subjects and patients with idiopathic pulmonary fibrosis (IPF)
• Who was studied: 43 sheep: 18 controls and 25 asbestos-exposed. Of the exposed sheep, 10 had normal chest X-rays (Group SA) and 15 had irregular interstitial opacities (Group SB). Humans: 30 asbestos workers aged 58 ± 4 years from the mines and mills of the Eastern Townships of Quebec, including 29 current or ex-smokers. The workers were split into Group A (13, no disease signs), Group B (7, abnormal gallium-67 scans and rigid pressure-volume curves) and Group C (10, asbestosis). Comparison groups were 11 normal nonsmokers and 9 patients with biopsy-proven IPF.
• Exposure: Sheep: 100 mg UICC chrysotile B asbestos in 100 ml phosphate-buffered saline, given by tracheal infusion every 2 weeks for 18 months. Control sheep received saline alone. Workers: chrysotile asbestos in mines and mills for an average of 33 ± 5 years.
• Main results:
  • Macrophage PA activity was higher in asbestos-exposed sheep than in control sheep: 87.2 ± 17.3 versus 41.1 ± 7.2 units per 10^5 alveolar macrophages per 24 hours (mean ± SE), p less than 0.05.
  • Macrophage PA in Group SB sheep (abnormal X-rays) was higher than in controls: 104.2 ± 27.8 versus 41.1 ± 7.2 units per 10^5 macrophages per 24 hours, p less than 0.02. Group SA sheep (normal X-rays) did not differ significantly from controls: 61.7 ± 8.8, p greater than 0.1.
  • Lavage fluid PA was higher in exposed sheep than in controls: 674.9 ± 168.4 versus 81.3 ± 19.7 units per milligram of albumin per 24 hours, p less than 0.01. Group SB was 906.4 ± 252.9 (p less than 0.001 versus control). Group SA was 327.5 ± 132.7, which did not reach statistical significance (p greater than 0.05).
  • Group A workers (no evidence of lung disease) had lavage PA similar to normal subjects: 97.9 ± 36.8 versus 102.3 ± 10.5 units per milligram of albumin per 24 hours, p greater than 0.20.
  • Group B workers (early lung disease: abnormal gallium-67 scan and rigid pressure-volume curves) had markedly higher lavage PA than normal subjects: 477.0 ± 171.0 versus 102.3 ± 10.5 units per milligram of albumin per 24 hours, p less than 0.01. They were also higher than Group A workers (p less than 0.01).
  • Group C workers (definite asbestosis) had lower lavage PA than Group B workers: 120.1 ± 20.7 versus 477.0 ± 171.0 units per milligram of albumin per 24 hours, p less than 0.05.
  • Patients with IPF had significantly lower lavage PA than normal subjects: 49.1 ± 10.3 versus 102.3 ± 10.5 units per milligram of albumin per 24 hours, p less than 0.05.
• The authors' conclusion: The authors concluded that early asbestos-induced alveolitis is associated with increased lung PA activity, whereas PA activity is normal in the more advanced forms of asbestosis. They stated that the mechanisms, and the role of PA in causing asbestosis, remain to be defined.
• Limitations the authors state:
  • The asbestos workers and the normal subjects differed markedly in smoking history and age. The authors argued that these differences were not related to the PA changes.
  • The cell source of the increased PA in the workers' lavage fluid is unknown, because several lung cell types can release PA.

Topics

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

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Interstitial Lung Disease, Idiopathic, Pulmonary Fibrosis, Asbestos Exposure, Bronchoalveolar Lavage (BAL), UICC, Chrysotile.

Related studies

• Macrophage plasminogen activator: induction by asbestos is blocked by anti-inflammatory steroids — J. Hamilton, J.D. Vassalli, et al. (1976)
• Induction of macrophage plasminogen activator by asbestos is independent of PKC activation — D. Lison, F. Raguzzi, et al. (1991)
• Expression of plasminogen activator and plasminogen activator inhibitor by rat mesothelioma induced by asbestos — S.P. Lenz, F.H. Green, et al. (1993)
• Increased alveolar nitric oxide concentration and high levels of leukotriene B(4) and 8-isoprostane in exhaled breath condensate in patients with asbestosis — H. Lehtonen, P. Oksa, et al. (2007)
• Alveolar macrophages from patients with asbestos exposure release increased levels of leukotriene B4 — J.G. Garcia, D.E. Griffith, et al. (1989)
• 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)

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