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Susceptibility of Cytokine-treated Lung Epithelial Cells to Particles:Influence of Organic Carbon Particle Content.
Citation:
DYE, J. A., N. MANZO, J. K. MCGEE, AND R. SLADE. Susceptibility of Cytokine-treated Lung Epithelial Cells to Particles:Influence of Organic Carbon Particle Content. Presented at American Association of Aerosol Research (AAAR), San Diego, CA, March 22 - 26, 2010.
Impact/Purpose:
This study demonstrates that differential response to air pollutants in healthy vs susceptible individuals (e.g., with asttham, bronchitis, or COPD) may relate, in part, to inability to effectively generate or maintain appropriate antioxidant responses to air pollutants.
Description:
Exposure of individuals with airways inflammatory disease (asthma, chronic bronchitis, COPD) to near-road air pollution correlates epidemiologically with deleterious health outcome. Associated pulmonary toxicity purportedly involves generation of reactive oxygen species (ROS) and activation of various local and systemic inflammatory pathways. We hypothesized that increased levels of inflammatory cytokines in the lung in some manner altered the ability of surface epithelial cells to withstand and adapt to ongoing exposure to near-road air pollutants such as diesel exhaust particles (DEP). The present study utilized alveolar type II-like epithelial cells (LA-4) pre-treated with exogenous cytokines to model an inflammatory lung microenvironment. To determine if the cytokine-treated cells were less able to endure exposure to the particles representative of near-road pollution, LA-4 cells were exposed to carbon black (CB), SRM 2975, or an automobile-generated sample, DEP-A. Based on changes in lactate dehydrogenase (LDH) release, heme oxygenase-l (HO-I) expression, and glutathione levels, data revealed that acute exposure to DEP-A (the sample highest in organic carbon), but not CB or SRM 2975, induced an oxidant burden that healthy epithelial cells were able to tolerate through effective cytoprotective and antioxidant responses. However, within the inflammatory microenvironment, DEP-A exposed cells were not able to maintain normal redox status, resulting in cellular oxidative stress and overt injury. Furthermore, the augmented injury of the inflamed cells following DEP-A exposure appeared to involve interactions between cellular production of nitric oxide and increased ROS production. Data suggest that health risk related to near-road air pollution exposure of individuals with inflammatory lung disorders involves a complex interplay between the radical-generating capacity of the particles and ongoing inflammatory processes, which combine to impede the ability of the lung to effectively adapt to additional particle-induced oxidative stress. (This abstract does not reflect US EPA policy. Funded by the EPA CT826512010.) (Words 328)