Increased production of plasminogen activator inhibitor in vitro by pleural leukocytes from rats intratracheally instilled with crocidolite asbestos

Our plain-English summary of Increased production of plasminogen activator inhibitor in vitro by pleural leukocytes from rats intratracheally instilled with crocidolite asbestos, by X.Y. Li, G.M. Brown, D. Lamb, et al (Environmental Research, 1991).

The study

• Authors: X.Y. Li, G.M. Brown, D. Lamb, K. Donaldson
• Journal: Environmental Research
• Published: 1991;55(2):135-44
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

We have previously reported that normal pleural leukocytes secrete a urokinase-type plasminogen activator inhibitor (PAI) in culture. In view of the pathogenic effects of asbestos on the pleura, in particular pleural fibrosis, we have extended these observations to crocidolite asbestos-exposed rats. Pleural leukocytes from rats exposed to crocidolite asbestos were found to secrete more PAI in culture than controls. The activity of PAI in pleural leukocyte-conditioned medium increased in a dose-dependent manner in relation to the quantity of asbestos injected into the lung. However, with increasing time post asbestos instillation, there was no significant change in the secretion of PAI by pleural leukocytes in culture compared with earlier time points of crocidolite-exposed rats. Plasminogen activator was not detectable in the conditioned medium at any time point. The data derived from this study may help to elucidate the pathogenesis of some pleural disorders caused by exposure to fibrous dusts in the lungs.

In plain English

This was an animal experiment. Rats had 1, 5 or 10 mg of crocidolite asbestos (UICC standard sample A) put directly into the windpipe. Control rats received salt solution only. The rats were killed 1, 3, 14 or 30 days later. White blood cells were washed out of the pleural space (the space around the lungs) and grown in culture. The authors tested whether fluid from these cells blocked urokinase, an enzyme that starts the breakdown of fibrin clots. That blocking is a sign of plasminogen activator inhibitor (PAI). After 5 mg, fluid from asbestos-exposed rats' cells blocked clot breakdown more than control fluid at every time point. There was no significant difference between time points. The effect rose with dose. With 1 mg, the difference from controls was significant only in the three least-diluted samples. With 5 and 10 mg, it was significant at every dilution. Plasminogen activator was not detected in any cell fluid. The authors concluded that there may be a localized fibrinolytic deficit in the pleura of asbestos-exposed lungs that could favor fibrogenesis.

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: rats were given crocidolite asbestos by intratracheal instillation, and their pleural leukocytes were then studied in culture (in vitro).
• Who was studied: PVG rats about 12 weeks old, bred at the Institute of Occupational Medicine Animal Unit, Edinburgh. There were 14 normal rats for baseline cell counts and 5 to 7 rats per asbestos group. Rats were killed 1, 3, 14 or 30 days after instillation.
• Exposure: Crocidolite asbestos (UICC standard sample A) at doses of 1, 5 or 10 mg in 0.5 ml PBS, instilled into the trachea. Control rats received 0.5 ml PBS alone.
• Main results:
  • In normal rats, more than 80% of pleural leukocytes were macrophages (82%, SEM 1.6). Mean total cell number was 4.51 (SEM 0.29) x 10^6, n = 14 rats.
  • One day after 1, 5 or 10 mg crocidolite, total pleural leukocyte numbers did not change. There was a minimal increase in the percentage of eosinophils, a consistent decrease in the percentage of macrophages, and a few neutrophils appeared at the highest dose.
  • After 5 mg crocidolite, total pleural cell number rose significantly from Day 3 through Day 30 (6.30, 6.92 and 6.96 x 10^6 on Days 3, 14 and 30, versus 4.51 x 10^6 in normal rats). The percentage of eosinophils also rose significantly between Days 3 and 30.
  • No plasminogen activator activity was detected in culture fluid from either control or asbestos-exposed pleural leukocytes.
  • After 5 mg crocidolite, culture fluid from pleural leukocytes showed markedly increased PAI activity at all time points (1 to 30 days) compared with controls. There was no significant difference between time points. Exceptions to significance were the 1:64 dilution for the 3-day group and the 1:16 dilution for the 14-day group.
  • One day after instillation, PAI activity rose with dose. For the 1 mg group, the difference from controls was significant only at dilutions 1:8, 1:4 and 1:2 (P < 0.05 to P < 0.01). For the 5 and 10 mg groups, all dilution points were significantly higher than controls (P < 0.01 to P < 0.001). At the higher dilutions, the 10 mg group was significantly higher than the 5 mg group (P < 0.001), and at 1:64 its inhibition was still nearly 50%.
  • The authors stated that the asbestos fibers did not move from the lung to the pleural space in detectable numbers. They cited ultrastructural studies and unpublished data for this.
• The authors' conclusion: The authors concluded that the study provided evidence suggesting a localized fibrinolytic deficit in the pleura of asbestos-exposed lungs, which could favor fibrogenesis. In their view, increased PAI would favor local build-up of fibrin that could act as a scaffold for fibroblasts and ultimately lead to fibrosis.
• Limitations the authors state:
  • Experimental variation may have masked differences between time points.
  • The authors did not measure plasminogen activator or PAI in alveolar leukocytes after asbestos deposition.
  • The roles of neutrophils, eosinophils and mast cells in asbestos-induced pleural inflammation remained unclear.

Topics

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

Medical terms in this study, explained in our Lexicon: Crocidolite, Pleura, Fibrosis.

Related studies

• Intratracheal injection of crocidolite asbestos depresses the secretion of tumor necrosis factor by pleural leukocytes in vitro — X.Y. Li, D. Lamb, et al. (1992)
• Expression of plasminogen activator and plasminogen activator inhibitor by rat mesothelioma induced by asbestos — S.P. Lenz, F.H. Green, et al. (1993)
• Production of interleukin 1 by rat pleural leucocytes in culture after intratracheal instillation of crocidolite asbestos — X.Y. Li, D. Lamb, et al. (1993)
• The production of TNF-alpha and IL-1-like activity by bronchoalveolar leucocytes after intratracheal instillation of crocidolite asbestos — X.Y. Li, D. Lamb, et al. (1993)
• 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)
• Post-transcriptional regulation of plasminogen activator inhibitor type-1 expression in human pleural mesothelial cells — S. Shetty, T. Velusamy, et al. (2010)

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