Role of nitric oxide in the progression of pneumoconiosis

Our plain-English summary of Role of nitric oxide in the progression of pneumoconiosis, by V. Castranova (Biochemistry. Biokhimii︠a︡, 2004).

The study

• Author: V. Castranova
• Journal: Biochemistry. Biokhimii︠a︡
• Published: 2004;69(1):32-7
• Type of article: Review
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Conflicting evidence has been reported as to whether nitric oxide (NO) possesses anti-inflammatory or inflammatory properties. Data are presented indicating that in vitro or in vivo exposure to selected occupational dusts, i.e., crystalline silica, organic dust contaminated with endotoxin, or asbestos, results in upregulation of inducible nitric oxide synthase (iNOS) and the production of NO by alveolar macrophages and pulmonary epithelial cells. Nitric oxide production is associated temporally and anatomically with pulmonary damage, inflammation, and disease progression in response to occupational dusts. Blockage of inducible nitric oxide synthase by administration of NOS inhibitors or in iNOS knockout mice decreases the magnitude of injury and inflammation following in vivo exposure to silica, endotoxin, or asbestos. Therefore, NO may play an important role in the initiation and progression of pneumoconiosis.

In plain English

This article was a review, not a new study. The author, at the National Institute for Occupational Safety and Health, summarized laboratory research on whether nitric oxide, a molecule made by lung cells, helps drive lung disease from three kinds of dust: crystalline silica, organic dusts contaminated with bacterial endotoxin (including cotton dust), and asbestos. The asbestos fiber type was not named. Studies cited in the review reported that asbestos increased nitric oxide production by lung cells grown in the laboratory, and increased the enzyme that makes it in rat lungs. One cited study found that asbestos raised this enzyme in rats but not in hamsters, and only the rats showed significant lung damage and inflammation. In a cited silica study, mice lacking the enzyme had 80% lower lesion number and size one week after exposure. Human data came from one volunteer per group: a healthy control and two exposed coal miners. The review also described evidence that nitric oxide can reduce inflammation. The author concluded that nitric oxide may play an important role in the start and progression of pneumoconiosis.

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 of published laboratory, animal and limited human studies (plus some unpublished data from the author's laboratory)
• Who was studied: The reviewed studies used cultured lung and macrophage cells, rats, mice, rabbits and hamsters. One cited human comparison used one healthy control and two coal miners, with a single volunteer in each group.
• Exposure: Crystalline silica, organic dusts contaminated with bacterial endotoxin (lipopolysaccharide, LPS), cotton dust, and asbestos (fiber type not specified). The review also covered coal mine dust, carbonyl iron and titanium dioxide in one comparison study.
• Main results:
  • Cited studies reported that asbestos placed into rat airways (intratracheal instillation) increased expression of inducible nitric oxide synthase (iNOS) in lung cells. Laboratory exposure of alveolar macrophages or lung epithelial cells to asbestos increased nitric oxide production.
  • In a cited comparison (Dorger et al.), asbestos increased iNOS in rats one day after treatment but failed to increase iNOS levels in hamsters. Rats showed neutrophil infiltration, damage to the alveolar air/blood barrier and edema. Asbestos did not significantly alter these measures in hamsters.
  • A cited study (Quinlan et al.) reported a timing correlation between nitric oxide production by alveolar macrophages and neutrophil infiltration into the lung after asbestos inhalation.
  • In rats given silica into the airways, iNOS mRNA in lavage cells was 1500% of control and nitric oxide-dependent chemiluminescence was 1750% of control, measured 24 hours after exposure (Table 1, from cited studies).
  • In a cited silica inhalation study (Srivastava et al.), lesion number and size were 80% lower in iNOS knockout mice than in wild type mice one week after exposure, with no progression through 12 weeks.
  • Nitric oxide-dependent chemiluminescence from lavaged alveolar macrophages, as percent of a healthy control (100), was 1520 in a coal mine dust-exposed miner with a normal X-ray and 3100 in one with an abnormal X-ray. Each group was a single volunteer.
  • Opposing evidence was also reviewed: in a cited rabbit study (Kang et al.), inhaled nitric oxide (10 ppm) significantly decreased lung damage and inflammation caused by intravenous LPS.
• The authors' conclusion: The author concluded that nitric oxide may play an important role in the initiation and progression of pneumoconiosis.
• Limitations the authors state:
  • The author noted that both anti-inflammatory and pro-inflammatory effects of nitric oxide have been reported, so its role in disease initiation and progression was unresolved.

Topics

Medical terms in this study, explained in our Lexicon: Pneumoconiosis, Crystalline, Inducible Nitric Oxide Synthase (iNOS), Alveolar Macrophage, Inflammation, Disease Progression.

Related studies

• Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis — H. Ohshima, H. Bartsch (1994)
• Dual role of inducible nitric oxide synthase in acute asbestos-induced lung injury — M. Dörger, A.M. Allmeling, et al. (2002)
• Participation of nitric oxide and iron in the oxidation of DNA in asbestos-treated human lung epithelial cells — C.C. Chao, S.H. Park, et al. (1996)
• Increased alveolar nitric oxide concentration and high levels of leukotriene B(4) and 8-isoprostane in exhaled breath condensate in patients with asbestosis — H. Lehtonen, P. Oksa, et al. (2007)
• Asbestos fibers and interferon-gamma up-regulate nitric oxide production in rat alveolar macrophages — G. Thomas, T. Ando, et al. (1994)
• Mechanisms of asbestos-induced nitric oxide production by rat alveolar macrophages in inhalation and in vitro models — T.R. Quinlan, K.A. BeruBe, et al. (1998)

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