Enhanced generation of free radicals from phagocytes induced by mineral dusts

Our plain-English summary of Enhanced generation of free radicals from phagocytes induced by mineral dusts, by V. Vallyathan, J.F. Mega, X. Shi, et al (American Journal of Respiratory Cell and Molecular Biology, 1992).

The study

• Authors: V. Vallyathan, J.F. Mega, X. Shi, N.S. Dalal
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1992;6(4):404-13
• Cited by: 151 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Several studies have suggested that pulmonary toxicity to asbestos and silica may be mediated through oxidant-induced cell injury. We have reported recently that surface radicals associated with freshly fractured silica may be an important factor in cell injury and induction of pulmonary disease. Although the generation of oxygenated radicals in dust-cell interactions has been demonstrated, there are no data correlating the toxicity of a dust with the level of oxygen radical generation by the dust during its interaction with phagocytic cells. In the present study, we have investigated the in vitro generation of oxygen free radicals from human neutrophils and rat alveolar macrophages stimulated with freshly fractured silica, aged silica, amosite, crocidolite, chrysotile, and nontoxic dust, barite. Electron spin resonance (ESR) with the aid of a spin trap phenyl-N-tert-butyl nitrone (PBN) was used to measure the oxygen radicals generated during phagocytosis of the dusts. The relative toxicity index and ESR peak heights, on an equal surface area basis and normalized to barite as one, showed a direct relationship. The normalized toxicity indices and peak heights were: silica, 3.5 versus 2; chrysotile, 4 versus 2; crocidolite, 11 versus 8; and amosite, 26 versus 13. Addition of hydroxyl radical scavengers such as catalase, dimethyl sulfoxide, 1,3 dimethyl-2-thiourea (DMTU), sodium benzoate, and mannitol prevented the radical generation. Carmustine, a glutathione reductase-glutathione peroxidase inhibitor, caused a 5-fold increase in the radical generation. These results indicate that a nontoxic dust such as barite generates toxic oxygen radicals at a minimal level that can be quenched by the normal cellular defense system. For toxic dusts such as silica, amosite, chrysotile, and crocidolite, the potential for oxygen radical generation is enhanced by their surface properties, physical dimensions, and the surface-based radical-generating redox sites. The enhanced radical generation may impair the cellular defense system, resulting in cell injury. Use of scavengers, chelators, and potentiating agents suggests the membrane-based oxidase system as the probable primary source of the radical-generating system. The data presented herein suggest the generation of oxygen free radicals as an important primary event in silica- as well as asbestos-induced cell injury.

In plain English

This laboratory (in vitro) study exposed human neutrophils from healthy volunteers and alveolar macrophages from rats to one of six dusts for one hour: freshly fractured silica, aged silica, amosite, crocidolite, chrysotile, or barite, which served as a nontoxic control. Particles were tested at 250 micrograms per milliliter and fibers at 50. Oxygen free radicals were measured by electron spin resonance. In neutrophils, barite did not differ significantly from cells without dust, while every other dust gave significantly larger signals than barite. The authors compared these signals with cell-toxicity data from earlier published studies. On an equal surface area basis, toxicity and radical signal showed a positive correlation. With barite set at 1, toxicity index versus signal was: silica 3.5 versus 2, chrysotile 4 versus 2, crocidolite 11 versus 8, and amosite 26 versus 13. On an equal mass basis there was no correlation. Catalase blocked about 85% of radical generation, and presoaking the dusts in iron chelators blocked about 80%. The authors concluded that radical production appears to be a primary event in silica- and asbestos-induced cell injury. They noted that the signals alone cannot positively identify the radical type.

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: In vitro laboratory experiment: cells exposed to mineral dusts, with oxygen free radicals measured by electron spin resonance (ESR) spin trapping using PBN
• Who was studied: Human polymorphonuclear neutrophils isolated from blood of healthy human volunteer donors, and alveolar macrophages obtained by lung lavage from male specific pathogen-free Sprague-Dawley rats. Numbers of donors and rats are not stated. Work was done at NIOSH and West Virginia University, Morgantown; no study dates are given.
• Exposure: Chrysotile (Quebec, Canada), amosite (Transvaal, South Africa) and crocidolite (Kalahari Desert, South Africa) fibers at 50 micrograms per ml. Crystalline silica, either freshly ground or 'aged' (stored at least 14 days), and barite (nontoxic control) at 250 micrograms per ml. All exposures were 1-hour incubations at 37 degrees C.
• Main results:
  • In neutrophils, barite (0.81 plus or minus 0.21 mm mean peak height, 5 experiments) was not significantly different from controls without dust (0.65 plus or minus 0.09 mm, 5 experiments).
  • In neutrophils, all three asbestos fibers gave significantly higher signals than barite: amosite 1.41 plus or minus 0.11 mm (4 experiments, p less than 0.05), chrysotile 1.45 plus or minus 0.15 mm (4 experiments, p less than 0.04), and crocidolite 2.07 plus or minus 0.33 mm (12 experiments, p less than 0.03).
  • Freshly fractured silica (2.08 plus or minus 0.46 mm, 4 experiments) produced more radicals than aged silica (1.12 plus or minus 0.04 mm, 3 experiments).
  • On an equal surface area basis, with barite set at 1, the toxicity index (derived from earlier published enzyme-release data) versus ESR peak height was: silica 3.5 versus 2, chrysotile 4 versus 2, crocidolite 11 versus 8, amosite 26 versus 13. The authors reported a positive correlation.
  • On an equal mass (1 mg) basis, toxicity and ESR peak heights did not correlate.
  • The radical-generating potential of the three fibers did not directly follow their total iron content (amosite about 34%, crocidolite about 18%, chrysotile less than 1%).
  • Presoaking the minerals in the iron chelators DETAPAC or deferoxamine inhibited radical generation by approximately 80%.
  • With crocidolite and neutrophils, catalase prevented approximately 85% of radical generation, while SOD was only 20% effective.
  • Preincubating cells with carmustine increased radical generation with crocidolite 5-fold, according to the text. The figure legend gives a different figure (see text_problems).
• The authors' conclusion: The authors concluded that production of oxygen free radicals appears to be an important primary event in silica- and asbestos-induced cell injury. They also concluded that the trapped species were mainly hydroxyl radicals, mostly derived from the cells' membrane-based oxidase system.
• Limitations the authors state:
  • The ESR signals alone cannot positively identify the trapped radical species, because the spin-trap spectra are nonspecific.
  • The radicals induced with carmustine gave a different spectrum, which the authors said needs further investigation.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Amosite, Chrysotile, Crocidolite.

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Amosite, Crocidolite, Chrysotile, Phagocytosis, Hydroxyl Radical, Glutathione (GSH).

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• Free radical generation in the toxicity of inhaled mineral particles: the role of iron speciation at the surface of asbestos and silica — I. Fenoglio, L. Prandi, et al. (2001)
• Distinctive profile of alveolar macrophage-derived cytokine release induced by fibrogenic and nonfibrogenic mineral dusts — I. Lemaire, S. Ouellet (1996)
• Cytokine and free radical responses of alveolar macrophages in vitro to asbestos fibres — L.C. Mongan, T. Jones, et al. (2000)

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