Inhibition of alveolar macrophage cytotoxicity by asbestos: possible role of prostaglandins

Our plain-English summary of Inhibition of alveolar macrophage cytotoxicity by asbestos: possible role of prostaglandins, by E. Bissonnette, B. Carré, C. Dubois, et al (Journal of Leukocyte Biology, 1990).

The study

• Authors: E. Bissonnette, B. Carré, C. Dubois, M. Rola-Pleszczynski
• Journal: Journal of Leukocyte Biology
• Published: 1990;47(2):129-34
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestosis and silicosis are chronic, fibrosing lung diseases due to prolonged inhalation of asbestos fibers or silica particles. However, little is known about the implication of these toxic dusts on cell-mediated cytotoxicity. Among the first types of cells that are in contact with the dusts are the alveolar macrophages (AM). We studied the effect of different concentrations of UICC chrysotile asbestos and silica on 18-h cytotoxicity of AM against tumor necrosis factor (TNF)-resistant P815 target cells or TNF-sensitive L929 target cells. Rat AM, obtained by bronchoalveolar lavage, were incubated for 2 h with 20, 50, or 100 micrograms/ml chrysotile or silica before the addition of target cells. AM cytotoxicity was significantly inhibited at greater than 20 micrograms/ml of chrysotile. In contrast, silica did not inhibit AM-mediated cytotoxicity at any concentration used. Asbestos, but not silica, caused significant production of PGE2 by macrophages and target cells. Addition of the cyclooxygenase inhibitor indomethacin to our system abolished all inhibition by asbestos. These results suggest that the inhibition of AM-mediated cytotoxicity by chrysotile was caused by prostaglandins, and that fibrogenic particles differ in their capacity to modulate AM function.

In plain English

This was a laboratory experiment using rat lung cells, not a study of people. The authors exposed alveolar macrophages (immune cells from the lung's air sacs), washed out of the lungs of male Wistar rats, to UICC chrysotile asbestos or to silica at 20, 50 or 100 micrograms per millilitre for 2 hours. They then measured how well the macrophages killed two kinds of laboratory-grown target cells: P815 mastocytoma cells and L929 fibroblast cells. Chrysotile significantly reduced the macrophages' killing of both target cell types at all three concentrations. Silica had no significant effect. The reduction by asbestos became non-significant, or was reversed, when indomethacin, a drug that blocks prostaglandin production, was added. Asbestos stimulated more production of the prostaglandin PGE2 by the macrophages than silica did. Asbestos, but not silica, also stimulated PGE2 production by both target cell lines. The authors concluded that asbestos inhibits rat macrophage killing activity by stimulating PGE2 production and that silica does not affect it. They suggested this difference may be relevant to the different lung cancer rates in asbestosis and silicosis.

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 rat alveolar macrophages and cultured target cell lines
• Who was studied: Alveolar macrophages obtained by bronchoalveolar lavage from male Wistar rats weighing 200 to 250 g. P815 mastocytoma cells and murine L929 fibroblast cells were used as targets. Each experiment was repeated four to six times, depending on the experiment.
• Exposure: UICC standard reference Chrysotile A asbestos fibers, and min-U-Sil-5 silica particles as a comparison, at 20, 50 and 100 micrograms per millilitre, with or without the prostaglandin-synthesis inhibitor indomethacin
• Main results:
  • Asbestos significantly inhibited macrophage killing of P815 target cells at all concentrations used (p less than 0.05 at 20, 50 and 100 micrograms per millilitre; six experiments). The inhibition became non-significant with indomethacin.
  • Silica had no significant effect at any concentration on macrophage killing of P815 cells
  • Asbestos significantly inhibited macrophage killing of L929 target cells (p less than 0.01 at 20, 50 and 100 micrograms per millilitre; five experiments). Indomethacin reversed this inhibition.
  • At 50 micrograms per millilitre, both dusts significantly increased TNF production by rat macrophages, more so with asbestos than with silica
  • Fiber-free fluid from macrophages pre-treated with 50 or 100 micrograms per millilitre asbestos inhibited the killing activity of fresh macrophages
  • Fiber-free fluid from asbestos-treated P815 cells strongly inhibited macrophage killing at all asbestos concentrations, but not when indomethacin was present during the pre-treatment
  • High concentrations of asbestos stimulated more PGE2 production by macrophages than silica did
  • Asbestos, but not silica, stimulated PGE2 production by the P815 and L929 target cells
  • At the highest particle concentration, 20% of macrophages died with asbestos and 30% with silica. The authors stated that this cell death alone did not explain the inhibition seen with asbestos.
• The authors' conclusion: The authors concluded that asbestos fibers inhibit rat macrophage killing activity by stimulating PGE2 production by different cell populations, and that silica does not affect it. They suggested this difference may be relevant to the different incidence of lung cancers in asbestosis and silicosis.
• Limitations the authors state:
  • The idea that asbestos stimulates mast cells to release prostaglandins was a hypothesis, based on a mastocytoma cell line. The authors said further experiments with lung mast cells were needed to confirm it.

Topics

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Silicosis, UICC, Chrysotile, Necrosis, Bronchoalveolar Lavage (BAL), PGE2, Macrophage.

Related studies

• Asbestos fibers and silica particles stimulate rat alveolar macrophages to release tumor necrosis factor. Autoregulatory role of leukotriene B4 — C.M. Dubois, E. Bissonnette, et al. (1989)
• Asbestos-stimulated tumour necrosis factor release from alveolar macrophages depends on fibre length and opsonization — K. Donaldson, X.Y. Li, et al. (1992)
• Interleukin 1 production and accessory cell function of rat alveolar macrophages exposed to mineral dust particles — Y. Oghiso, Y. Kubota (1987)
• Heterogeneity in immunologic functions of rat alveolar macrophages--their accessory cell function and IL-1 production — Y. Oghiso (1987)
• Response of perifused alveolar macrophages to glass fibers: effect of exposure duration and fiber length — G. Forget, M.J. Lacroix, et al. (1986)
• Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis — I. Lemaire, H. Beaudoin, et al. (1986)

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