Iron and reactive oxygen species in the asbestos-induced tumor necrosis factor-alpha response from alveolar macrophages

Our plain-English summary of Iron and reactive oxygen species in the asbestos-induced tumor necrosis factor-alpha response from alveolar macrophages, by P.P. Simeonova, M.I. Luster (American Journal of Respiratory Cell and Molecular Biology, 1995).

The study

• Authors: P.P. Simeonova, M.I. Luster
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1995;12(6):676-83
• Cited by: 117 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Free radicals and other reactive oxygen species (ROS) are important mediators in asbestos-induced lung toxicity. Asbestos fibers are thought to stimulate cells to generate ROS via iron that is present on fibrous silicates. The pathophysiologic responses in the lung after asbestos exposure are characterized by the accumulation of macrophages at the site of fiber deposition and the release of growth factors and proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha). We have examined the role of iron-catalyzed ROS in asbestos induction of TNF-alpha from rat alveolar macrophages. Treatment of alveolar macrophage cultures with asbestos stimulated dose-dependently TNF-alpha secretion, which was inhibited by the addition of deferoxamine, an iron chelator. Asbestos fibers, pretreated with deferoxamine to remove iron from the fibers before addition to alveolar macrophages, also significantly reduced the TNF-alpha response. Consistent with the role of iron on asbestos fibers in catalyzing hydroxyl radical generation, membrane-permeable hydroxyl radical scavengers (tetramethylthiourea, dimethyl sulfoxide) inhibited the asbestos-induced TNF-alpha response. The asbestos-induced increase in TNF-alpha, as well as in interleukin-1 alpha, and their inhibition by tetramethylthiourea occurred at the transcriptional level. The role of ROS in signaling TNF-alpha stimulation was confirmed by use of free radical-generating systems (hypoxanthine-xanthine oxidase, hydrogen peroxide, glucose-glucose oxidase, or ferrous plus hydrogen peroxide). These results suggest that intracellularly generated ROS can stimulate TNF-alpha in alveolar macrophages and that asbestos-induced TNF-alpha gene expression and secretion are mediated by iron-catalyzed product of ROS.

In plain English

This was a laboratory study of rat lung cells, not of people. The authors collected alveolar macrophages, a type of immune cell, by washing out the lungs of adult F344/N rats. They exposed the cells in culture dishes to chrysotile asbestos, crocidolite asbestos or titanium dioxide dust. Both asbestos types raised the cells' release of TNF-alpha, an inflammation signal, and more fiber produced more TNF-alpha. Crocidolite was considerably more potent than chrysotile. Titanium dioxide did not stimulate TNF-alpha secretion at any concentration tested. Deferoxamine, a chemical that binds iron, reduced the asbestos response. Stripping iron from the fibers beforehand cut it by approximately 50%. Chemicals that neutralize hydroxyl radicals (reactive forms of oxygen) and can enter cells also suppressed it, while catalase and SOD, which cannot enter cells, did not. After 18 hours, asbestos raised gene activity for TNF-alpha about 13-fold and for interleukin-1 alpha about 10-fold. The authors concluded that free radicals produced by iron-catalyzed reactions mediate asbestos-induced TNF-alpha gene expression and secretion. They noted that deferoxamine may not remove all iron from the fibers.

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 cells
• Who was studied: Alveolar macrophages collected by washing out the lungs (bronchoalveolar lavage) of adult F344/N rats and grown in culture
• Exposure: Chrysotile asbestos (Plastibest-20, originally from the Jeffrey mine in Quebec, Canada), crocidolite asbestos (ML-6, from a mine in South Africa) and titanium dioxide as a comparison dust. Crocidolite at 50 micrograms per ml was used for most later experiments. The authors also used chemical systems that generate reactive oxygen species, such as hydrogen peroxide and ferrous sulfate.
• Main results:
  • Both chrysotile and crocidolite raised TNF-alpha secretion from the rat macrophages as concentration increased. Crocidolite was considerably more potent than chrysotile.
  • Titanium dioxide did not stimulate TNF-alpha secretion at any concentration tested
  • Cell damage, measured by LDH release, accompanied the asbestos TNF-alpha response except at the lowest fiber concentrations
  • Adding the iron-binding chemical deferoxamine to the cultures caused a dose-dependent reduction in asbestos-induced TNF-alpha
  • Pretreating the fibers with deferoxamine to remove iron reduced asbestos-induced TNF-alpha secretion by approximately 50%
  • TMTU and DMSO, hydroxyl radical scavengers that enter cells, suppressed asbestos-induced TNF-alpha
  • Catalase and SOD, antioxidants that cannot enter cells, did not reduce TNF-alpha and were slightly stimulatory
  • Hydrogen peroxide combined with ferrous sulfate, which generates hydroxyl radicals, produced a stronger TNF-alpha response than hydrogen peroxide alone
  • After 18 hours, asbestos raised TNF-alpha gene transcripts approximately 13-fold and interleukin-1 alpha transcripts approximately 10-fold. With TMTU, transcript levels were similar to controls.
• The authors' conclusion: The authors concluded that reactive oxygen species are responsible for TNF-alpha production in alveolar macrophages, and that free radicals produced by iron-catalyzed reactions mediate asbestos-induced TNF-alpha gene expression and secretion.
• Limitations the authors state:
  • The authors suggested that deferoxamine does not remove all iron from the fibers, which may explain why it did not completely abolish the TNF-alpha response
  • The authors noted that ferryl radicals may also have been generated, in addition to hydroxyl radicals

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Jeffrey mine, Asbestos, Quebec

All asbestos mines

Topics

Medical terms in this study, explained in our Lexicon: Reactive Oxygen Species (ROS), Tumor Necrosis Factor-alpha (TNF-α), Alveolar Macrophage, Silicate, Asbestos Exposure, Macrophage, Deposition, Cytokine.

Related studies

• Asbestos fibres and man made mineral fibres: induction and release of tumour necrosis factor-alpha from rat alveolar macrophages — A.G. Ljungman, M. Lindahl, et al. (1994)
• Bidirectional modulation of TNF-alpha production by alveolar macrophages in asbestos-induced pulmonary fibrosis — S. Ouellet, H. Yang, et al. (1993)
• The latent form of TGFbeta(1) is induced by TNFalpha through an ERK specific pathway and is activated by asbestos-derived reactive oxygen species in vitro and in vivo — D.E. Sullivan, M. Ferris, et al. (2008)
• Synergistic effects of mineral fibres and cigarette smoke on the production of tumour necrosis factor by alveolar macrophages of rats — Y. Morimoto, M. Kido, et al. (1993)
• 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)
• Role of transcription factor NF-kappaB in asbestos-induced TNFalpha response from macrophages — N. Cheng, X. Shi, et al. (1999)

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