Contribution of reactive oxygen and nitrogen species to particulate-induced lung injury

Our plain-English summary of Contribution of reactive oxygen and nitrogen species to particulate-induced lung injury, by S. Zhu, M. Manuel, S. Tanaka, et al (Environmental Health Perspectives, 1998).

The study

• Authors: S. Zhu, M. Manuel, S. Tanaka, N. Choe, E. Kagan, S. Matalon
• Journal: Environmental Health Perspectives
• Published: 1998;106 Suppl 5(Suppl 5):1157-63
• Type of article: Review
• Cited by: 44 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Recently, a second pathway for the generation of potential oxidants with the reactivity of the hydroxyl radical without the need for metal catalysis has been described. In response to various inflammatory stimuli, lung endothelial, alveolar, and airway epithelial cells, as well as activated alveolar macrophages, produce both nitric oxide (.NO) and superoxide anion radicals (O2.-). .NO regulates pulmonary vascular and airway tone and plays an important role in lung host defense against various bacteria. However, .NO may be cytotoxic by inhibiting critical enzymes such as mitochondrial aconitase and ribonucleotide reductase, by S-nitrosolation of thiol groups, or by binding to their iron-sulfur centers. In addition, .NO reacts with O2.- at a near diffusion-limited rate to form the strong oxidant peroxynitrite (ONOO-), which can nitrate and oxidize key amino acids in various lung proteins such as surfactant protein A, and inhibit their functions. The presence of ONOO- in the lungs of patients with acute respiratory distress syndrome has been demonstrated by measuring levels of nitrotyrosine, the stable product of tyrosine nitration. Various studies have shown that inhalation or intratracheal instillation of various respirable mineral dusts or asbestos fibers increased levels of inducible nitric oxide synthase mRNA. In this presentation, we review the evidence for the upregulation of .NO in the lungs of animals exposed to mineral particulates and assess the contribution of reactive nitrogen species in the pathogenesis of the resultant lung injury.

In plain English

This was a review paper based on a conference presentation. The authors summarised the basic chemistry of reactive oxygen species (superoxide anion, hydrogen peroxide, hydroxyl radical formed through Fenton/Haber-Weiss reactions) and of reactive nitrogen species, in which nitric oxide reacts with superoxide to form peroxynitrite, an oxidant that nitrates tyrosine residues in proteins such as surfactant protein A and can inhibit their function. They then reviewed published evidence that mineral dusts and asbestos fibers upregulate nitric oxide production in lung cells and animals. Among the work reviewed was the authors' own recent study, in which rats were exposed intermittently over two weeks to chrysotile or crocidolite fibers or to filtered air and sacrificed at 1 or 6 weeks after exposure; at 1 week more alveolar and pleural macrophages from asbestos-exposed rats showed iNOS protein, and nitrotyrosine was seen in asbestos-exposed lungs at both 1 and 6 weeks (chrysotile 84 ± 12 pmol/mg protein; crocidolite 59 ± 5; sham filtered air 31 ± 3.6; means ± 1 SEM; n = 3). The authors concluded that reactive nitrogen species may offer an alternative mechanism of asbestos-induced injury to Fenton reactions.

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: narrative review based on a conference presentation (also describing the authors' own previously reported rat inhalation study)
• Who was studied: Published studies of lung cells, cultured macrophages and mesothelial cells, and animals (mainly rats) exposed to mineral dusts and asbestos; the authors' own cited study used rats exposed intermittently over 2 weeks to chrysotile or crocidolite or filtered air and sacrificed at 1 or 6 weeks
• Exposure: Asbestos fibers, described as three commercially used varieties: chrysotile (a serpentine asbestos) and the amphiboles crocidolite and amosite; other mineral dusts (silica, coal mine dust) and comparison particles (carbonyl iron, titanium dioxide) were also discussed
• Main results:
  • In the authors' cited rat study, lung nitrotyrosine (a marker of peroxynitrite formation) was greater in asbestos-exposed than sham-exposed rats
  • In the same rat study, iNOS immunoreactivity in alveolar and pleural macrophages was greater at 1 week in asbestos-exposed rats
  • In the same rat study, nitrotyrosine was present in lungs of chrysotile- and crocidolite-exposed rats at both 1 and 6 weeks
  • Reviewed work: both crocidolite and chrysotile upregulated nitric oxide production by cultured rat alveolar macrophages in the presence of IFN-gamma
  • Reviewed work: in the same macrophage study, carbonyl iron, a nonfibrogenic particulate, did not induce nitric oxide formation
  • Reviewed work: in cultured rat pleural mesothelial cells combined with interleukin-1, nitric oxide formation was stimulated more by chrysotile than by crocidolite, and not by carbonyl iron
  • The authors noted that iron content alone does not explain fibrogenicity, since crocidolite contains about 18 times the elemental iron of chrysotile
• The authors' conclusion: The authors concluded that chrysotile and crocidolite induce reactive nitrogen species in vivo, which may provide a mechanism of asbestos-induced injury alternative to Fenton reactions

Topics

Medical terms in this study, explained in our Lexicon: Hydroxyl Radical, Alveolar Macrophage, Superoxide, Peroxynitrite, Tyrosine Nitration, Inducible Nitric Oxide Synthase (iNOS), Reactive Nitrogen Species (RNS).

Related studies

• Asbestos fibers and interleukin-1 upregulate the formation of reactive nitrogen species in rat pleural mesothelial cells — N. Choe, S. Tanaka, et al. (1998)
• Mobilization of iron from urban particulates leads to generation of reactive oxygen species in vitro and induction of ferritin synthesis in human lung epithelial cells — K.R. Smith, A.E. Aust (1997)
• Pulmonary oxidative stress, inflammation and cancer: respirable particulate matter, fibrous dusts and ozone as major causes of lung carcinogenesis through reactive oxygen species mechanisms — A. Valavanidis, T. Vlachogianni, et al. (2013)
• Reactive oxygen species: their relation to pneumoconiosis and carcinogenesis — V. Vallyathan, X. Shi, et al. (1998)
• Carbon nanotubes induce inflammation but decrease the production of reactive oxygen species in lung — D. Crouzier, S. Follot, et al. (2010)
• Interactions of exogenous or evoked agents and particles: the role of reactive oxygen species — A. Churg (2003)

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