Lung exposure to mineral dusts enhances the capacity of lung inflammatory cells to release superoxide

Our plain-English summary of Lung exposure to mineral dusts enhances the capacity of lung inflammatory cells to release superoxide, by A. Cantin, F. Dubois, R. Bégin (Journal of Leukocyte Biology, 1988).

The study

• Authors: A. Cantin, F. Dubois, R. Bégin
• Journal: Journal of Leukocyte Biology
• Published: 1988;43(4):299-303
• Cited by: 44 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In vitro exposure of macrophages and neutrophils to inorganic dusts can enhance their oxidative metabolism, however the effects of inorganic dust inhalation on lung-inflammatory cell-oxidative metabolism remain unknown. To address this issue, we studied the superoxide anion release from lung inflammatory cells obtained by bronchoalveolar lavage from 19 sheep exposed repeatedly to UICC chrysotile B asbestos (100 mg) over an 18 month period and 10 sheep exposed to a single exposure of quartz (100 mg) over a 6 month period. Exposure to asbestos and quartz did not induce an increase in the spontaneous release of superoxide from inflammatory cells. However lung-inflammatory cells from sheep exposed to asbestos released much higher levels of superoxide in the presence of phorbol myristate acetate (PMA) than did cells of unexposed sheep. In quartz exposed animals, superoxide release with PMA stimulation remained significantly increased up to 2 months after a single quartz infusion. These results suggest that inorganic dust inhalation primes lung inflammatory cells in vivo and markedly enhances their capacity to release toxic oxygen radicals.

In plain English

In this animal experiment at the Université de Sherbrooke, Quebec, 19 sheep had 100 mg of UICC chrysotile B asbestos infused into the windpipe every 2 weeks for 18 months, while 10 control sheep received saline. In a second model, 10 sheep received one 100 mg dose of quartz into the tracheal lobe of the lung and 10 controls received saline. These sheep were followed for 6 months. Cells washed from the lungs (bronchoalveolar lavage) were tested for release of superoxide, a toxic form of oxygen. Without stimulation, release was not increased in either exposed group. When stimulated with PMA, cells from asbestos-exposed sheep released about three times as much as control cells at month 6 (14.9 versus 5.4 nmol cytochrome-c per million cells per hour, p less than 0.01), and stayed higher throughout. Cells from quartz-exposed sheep showed a similar increase up to two months, returning to levels similar to controls after 6 months. In asbestos-exposed sheep, lung cell numbers rose significantly only at months 9 and 18. The authors concluded that dust exposure activated lung inflammatory cells, mostly macrophages, markedly enhancing their capacity to release superoxide.

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: Animal experiment: two experimental models of dust exposure in sheep (repeated low-dose chrysotile asbestos; single high-dose quartz), each with saline-treated controls, with repeated bronchoalveolar lavage
• Who was studied: Sheep weighing 25-40 kg, studied at the Unité de Recherche Pulmonaire, Université de Sherbrooke, Québec, Canada. Asbestos model: 29 sheep (19 exposed, 10 saline controls). Quartz model: 20 sheep (10 exposed, 10 saline controls). Study dates not given.
• Exposure: Asbestos model: 100 mg UICC chrysotile B asbestos in 100 ml saline given by intratracheal infusion every 2 weeks for 18 months. Quartz model: a single 100 mg dose of quartz in 100 ml saline infused into the tracheal lobe, followed monthly for 6 months.
• Main results:
  • Spontaneous (unstimulated) superoxide release from lung inflammatory cells was not increased in asbestos-exposed sheep, nor at any time in quartz-exposed sheep
  • With PMA stimulation, cells from asbestos-exposed sheep released threefold more superoxide than cells from unexposed controls at month 6 (14.9 ± 1.8 vs 5.4 ± 1.2 nmol cytochrome-c per 10^6 cells per hour, p < 0.01, means ± standard error), and release remained increased throughout the study period
  • In quartz-exposed sheep, PMA-stimulated superoxide release was similarly increased up to two months after the single instillation, then decreased and returned to values similar to controls after 6 months
  • In asbestos-exposed sheep, lavage cell numbers did not increase within the first 6 months. Significant increases in total cells, macrophages and PMNs occurred at months 9 and 18. Total cells were 16.66 at month 0, 28.11 at month 9 and 35.57 at month 18, in units of 10^4 per ml.
  • Quartz-exposed sheep developed an alveolitis with marked increases in total cells, macrophages and PMN cells. These changes appeared early (1 month) and persisted throughout the 6-month study period.
  • In both asbestos- and silica-exposed sheep, the enhanced PMA-stimulated superoxide release did not correlate with the percentage of PMNs in the lavage cell counts
• The authors' conclusion: The authors concluded that dust exposure of the lower respiratory tract in vivo activates resident alveolar inflammatory cells, mostly macrophages, by markedly enhancing their superoxide-releasing capacity. They considered this consistent with the concept that lung inflammatory cell activation has a major role in the pneumoconioses. In the asbestos model, the enhanced capacity preceded changes in inflammatory cell numbers.
• Limitations the authors state:
  • The relative contribution of alveolar macrophages and lung PMNs to the enhanced release was not clear
  • Whether the enhanced release is mediated by changes in NADPH oxidase kinetics remains unknown
  • The consequences of the enhanced oxidant burden for the dust-related lung diseases remain unknown

Topics

Medical terms in this study, explained in our Lexicon: Superoxide, Macrophage, Bronchoalveolar Lavage (BAL), UICC, Chrysotile.

Related studies

• Measurement of reactive oxygen metabolites produced by human monocyte-derived macrophages exposed to mineral dusts — P. Nyberg, M. Klockars (1990)
• Dehydroepiandrosterone inhibits the spontaneous release of superoxide radical by alveolar macrophages in vitro in asbestosis — W.N. Rom, T. Harkin (1991)
• Relationship of inflammatory cell cytokines to disease severity in individuals with occupational inorganic dust exposure — W.N. Rom (1991)
• IgG specifically enhances chrysotile asbestos-stimulated superoxide anion production by the alveolar macrophage — R.K. Scheule, A. Holian (1989)
• 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)
• Pulmonary mineral dust. A study of ninety patients by electron microscopy, electron microanalysis, and electron microdiffraction — J.P. Berry, P. Henoc, et al. (1976)

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