Interactions of exogenous or evoked agents and particles: the role of reactive oxygen species.
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.
Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada. achug@interchange.ubc.ca
Andrew
A
Churg
D000393:Air Pollutants / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008171:Lung Diseases / Q000209:etiology / Q000378:metabolism*; D018384:Oxidative Stress; D010126:Ozone / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects
D000393:Air Pollutants; D017382:Reactive Oxygen Species; D010126:Ozone