Fibrinolysis by rat mesothelial cells in vitro: the effect of mineral dusts at non-toxic doses

Our plain-English summary of Fibrinolysis by rat mesothelial cells in vitro: the effect of mineral dusts at non-toxic doses, by K. Donaldson, G.M. Brown, R.E. Bolton, et al (British Journal of Experimental Pathology, 1988).

The study

• Authors: K. Donaldson, G.M. Brown, R.E. Bolton, J.M. Davis
• Journal: British Journal of Experimental Pathology
• Published: 1988;69(4):487-94
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Rat mesothelial cell cultures were shown to have considerable plasminogen dependent and independent fibrinolytic activity in vitro using an 125I fibrin degradation assay. At non-toxic doses of the mineral dusts titanium dioxide, quartz and crocidolite asbestos, as assessed by 51Cr release, the fibrinolytic activity of mesothelial cells was inhibited. Quartz had the greatest inhibitory effect and crocidolite asbestos had the least. These results suggests that inhibition of mesothelial cell fibrinolysis does not, on its own, explain pleural fibrosis due to toxic mineral dusts.

In plain English

This was a laboratory study of cells grown in dishes, not of people. The authors took mesothelial cells (the cells lining body cavities) from the peritoneal cavity of female rats and measured how well the cells broke down fibrin, a clotting protein, with and without added plasminogen. The cells broke down significantly more fibrin than the spontaneous background release, and more when plasminogen was added. The cells were then exposed to 1 to 3 micrograms per well of titanium dioxide, quartz or crocidolite asbestos, doses that did not significantly increase cell bursting, measured by release of a radioactive chromium label. All three dusts reduced plasminogen-dependent fibrin breakdown at some doses. For crocidolite this was significant only at 2 micrograms per well. Quartz had the greatest inhibitory effect and crocidolite the least. Titanium dioxide, a dust that does not cause fibrosis, also had this effect. The authors therefore concluded that reduced fibrin breakdown at non-toxic doses does not, on its own, explain pleural fibrosis in asbestosis and silicosis. The methods section names the asbestos as chrysotile, which conflicts with the rest of the article.

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: laboratory (in vitro) experiment on cultured rat mesothelial cells
• Who was studied: Mesothelial cells from the peritoneal cavity of female HAN/SPF rats aged 12 weeks; the number of rats and the dates are not given
• Exposure: Titanium dioxide (rutile form), DQ12 standard quartz and crocidolite asbestos (the methods list says chrysotile asbestos, UICC standard sample A), added at 1 to 3 micrograms per well. In preliminary experiments, doses of 10 micrograms per well and above were toxic to the cells.
• Main results:
  • Rat mesothelial cells broke down significantly more fibrin than the spontaneous release of label (printed as 'P < O.OOI', which reads as P less than 0.001 after correcting the scanning). Breakdown was significantly greater with plasminogen than without it at 5 h and 24 h (P less than 0.05).
  • At 1 to 3 micrograms per well, none of the dusts caused a significant increase in 51Cr release over 24 h. The authors used 51Cr release as their index of cell lysis (cells bursting).
  • Plasminogen-dependent fibrin breakdown was significantly reduced at 1 microgram per well with quartz, at 2 micrograms per well with all three dusts, and at 3 micrograms per well with quartz and titanium dioxide. Crocidolite at 3 micrograms per well reduced breakdown, but the reduction was not statistically significant.
  • Plasminogen-dependent activity is given as mean (standard error) counts per minute of dissolved labelled fibrin. Control cells: 17 916 (1707). At 2 micrograms per well: titanium dioxide 13 514 (1148), quartz 12 161 (1103), crocidolite 15 711 (1716). Crocidolite at 1 and 3 micrograms per well: 18 463 (1635) and 16 810 (1593).
  • Plasminogen-independent fibrin breakdown was reduced only by quartz at 2 and 3 micrograms per well (P less than 0.01 and P less than 0.05) and by crocidolite at 2 micrograms per well (P less than 0.05).
  • Of the three dusts, quartz had the greatest inhibitory effect and crocidolite asbestos the least.
• The authors' conclusion: The authors concluded that inhibition of mesothelial fibrin breakdown by low, non-lethal dust doses does not explain why asbestosis and silicosis produce fibrous pleural lesions while titanium dioxide exposure does not, because titanium dioxide also inhibited fibrin breakdown. They added that inhibition may contribute to pleural fibrosis, but other biological activities of dusts are almost certainly important.
• Limitations the authors state:
  • The authors could not rule out that toxic dusts reach a higher effective dose in the pleura than inert dust, because toxic dust may be harder to clear where fibrin has formed.
  • The authors could not tell whether the inhibition reflected a general non-lethal toxicity to the cells or a specific effect on fibrin breakdown.

Topics

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

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

Related studies

• The ability of inflammatory bronchoalveolar leucocyte populations elicited with microbes or mineral dust to injure alveolar epithelial cells and degrade extracellular matrix in vitro — K. Donaldson, J. Slight, et al. (1988)
• Interleukin 1 production and accessory cell function of rat alveolar macrophages exposed to mineral dust particles — Y. Oghiso, Y. Kubota (1987)
• Induction of metaphase and anaphase/telophase abnormalities by asbestos fibers in rat pleural mesothelial cells in vitro — M. Yegles, L. Saint-Etienne, et al. (1993)
• Cytotoxic action of mineral dusts on CHV 79 cells in vitro: factors affecting toxicity — S.O. Lock, M. Chamberlain (1983)
• The chemiluminescent response of human phagocytic cells to mineral dusts — I.P. Gormley, M.J. Kowolik, et al. (1985)
• Evaluation of the exposure, dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos in a 90-day quantitative inhalation toxicology study - Interim results Part 1: Experimental design, aerosol exposure, lung burdens and BAL — D.M. Bernstein, B. Toth, et al. (2020)

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