Interactions of exogenous or evoked agents and particles: the role of reactive oxygen species

Our plain-English summary of Interactions of exogenous or evoked agents and particles: the role of reactive oxygen species, by A. Churg (Free Radical Biology & Medicine, 2003).

The study

• Author: A. Churg
• Journal: Free Radical Biology & Medicine
• Published: 2003;34(10):1230-5
• Type of article: Review
• Cited by: 37 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Humans are commonly exposed to combinations of particles (occupational or environmental) and exogenous agents such as ozone and cigarette smoke that generate reactive oxygen species (ROS). Particles also evoke production of ROS from inflammatory cells and of mediators such as TNF-alpha that operate through ROS-related mechanisms. The interactions of particles and ROS-generating agents have been little explored. Adhesion of particles to the surface of pulmonary epithelial cells is increased by exposure to cigarette smoke, ozone, and TNF-alpha. Cigarette smoke and ozone increase the uptake of particles by epithelial cells, and both adhesion and uptake can be decreased by scavengers of ROS. Increased adhesion and uptake probably lead to increased levels of inflammatory and fibrogenic mediator production, and cigarette smoke definitely increases whole lung particle retention and enhances the fibrogenic effects of asbestos. In experimental models, the combination of particles plus ozone, cigarette smoke, or reagent hydrogen peroxide augments the inflammatory response to particles, increases cell proliferation, and leads to liberation of increased levels of chemoattractant mediators as well as vascular mediators such as endothelin. The small airways appear to be particular targets of coexposure to smoke or ozone and particles, a phenomenon that may produce chronic airflow obstruction.

In plain English

This short review appeared in a journal series on reactive oxygen species in lung disease. It mainly reviewed earlier laboratory and animal work, much from the author's laboratory, plus one uncited explant experiment. That research combined particles such as amosite asbestos, titanium dioxide and urban air particles with cigarette smoke, ozone, hydrogen peroxide or TNF-alpha. Earlier work found brief cigarette smoke exposure before amosite roughly doubled the number of fibers sticking to rat tracheal lining, compared with amosite alone. Brief smoke or ozone increased particle uptake by airway cells; the smoke effect persisted with dust given 48 hours later. Smoke-exposed animals retained more asbestos fibers in the lung; human smokers retained more in airway mucosa. Amosite plus six months of smoke synergistically increased lung hydroxyproline and bronchiolar wall thickness. An uncited experiment found hydrogen peroxide followed by urban air particles increased cytokine mediator gene expression. The author concluded that, where disease outcomes have been measured, combined exposures increase fibrotic responses. The author noted that such interactions had augmented cytokine generation even with titanium dioxide, but whether this holds for all low-toxicity particles was unexplored.

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: Review (part of a journal series of reviews), mainly of earlier studies; it also describes one uncited rat tracheal explant experiment
• Who was studied: Studies reviewed included rat tracheal explants in organ culture, experimental animals, cultured lung cells, and human smokers
• Exposure: Particles (amosite asbestos, titanium dioxide, residual oil fly ash, Ottawa urban air particles, and in one reviewed study chrysotile or soot) combined with cigarette smoke, ozone, hydrogen peroxide or TNF-alpha
• Main results:
  • In an earlier study from the author's group, brief cigarette smoke exposure of rat tracheal explants before amosite roughly doubled the number of adherent fibers compared with amosite alone. The effect was abolished by deferoxamine and partially reduced by catalase.
  • In tracheal explants, pretreatment with TNF-alpha increased adhesion of several particle types to airway cells.
  • A 10-minute exposure to cigarette smoke or ozone increased uptake of amosite and titanium dioxide by tracheal explant cells over 7 days. The smoke effect persisted with a 48-hour gap before dust exposure.
  • In experimental animals, coexposure to cigarette smoke increased whole-lung asbestos fiber retention and penetration into small airway walls. Human smokers retained more asbestos fibers in their airway mucosa.
  • A single dose of amosite followed by 6 months of cigarette smoke exposure produced synergistic increases in total lung hydroxyproline and bronchiolar wall thickness (author's earlier study).
  • In an uncited experiment described by the author, a 2-hour hydrogen peroxide exposure of rat tracheal explants followed by urban air particles and 7 days of culture increased gene expression of various cytokine mediators. The increases were synergistic for some, such as MCP-1.
  • In reviewed work by another group, amosite plus cigarette smoke extract caused synergistic increases in a laboratory measure of cell injury.
  • In reviewed work by another group, coexposure to urban air particles plus ozone produced synergistic increases in mediators including endothelin-1.
• The authors' conclusion: The author concluded that, where disease outcomes have been measured, combined exposures increase fibrotic responses, with small airways as particular targets. The author suggested that scavenging reactive oxygen species may be a useful approach to reducing disease.
• Limitations the authors state:
  • The author stated it has not been explored whether the augmentation of adverse effects (such as inflammatory cytokine generation) seen with titanium dioxide holds for all particles that have low toxicity on their own.
  • The author stated that the mechanism by which hydroxyl radical increases particle adhesion is not known.

Topics

Medical terms in this study, explained in our Lexicon: Reactive Oxygen Species (ROS), Fibrogenic, Obstructive Lung Disease.

Related studies

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• Increased mineral dust-induced production of reactive oxygen species by blood monocytes from patients with malignant diseases — P.W. Nyberg, S.A. Nordman, et al. (1994)
• Contribution of reactive oxygen and nitrogen species to particulate-induced lung injury — S. Zhu, M. Manuel, et al. (1998)

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