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Susceptibility of inflamed ariway and alveolar epithelial cells to injury induced by diesel exhaust particles of varying organic carbon content
Citation:
MANZO, N., R. SLADE, J. E. RICHARDS, L. Martin, AND J. A. DYE. Susceptibility of inflamed ariway and alveolar epithelial cells to injury induced by diesel exhaust particles of varying organic carbon content. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH - PART A: CURRENT ISSUES. Taylor & Francis, Inc., Philadelphia, PA, 73(8):565-580, (2010).
Impact/Purpose:
The purpose of this study was to create an in vitro cell culture system that models the adverse effects individuals with pre-existing pulmonary diseases, like asthma, may experience upon exposure to near-roadway generated particulate matter (PM). Using pulmonary epithelial cells the in vitro equivalent of low-grade pulmonary inflammation was modeled via treatment with a combination of exogenous pro-inflammatory cytokines normally found elevated in asthmatic lungs.
Description:
Exposure to traffic-related ambient air pollution, such as diesel exhaust particles (DEP), is associated with adverse health outcomes, especially in individuals with preexisting inflammatory respiratory diseases. Using an analogous in vitro system to model both the healthy and asthmatic lung the susceptibility of epithelial cells exposed to DEP of varying organic carbon composition was studied. Murine LA-4 alveolar type II-like epithelial cells, as well as primary murine tracheal epithelial cells (MTE), were treated with exogenous cytokines (TNFa + IL-l J3 + IFNy) to model a state of mild inflammation. These inflamed epithelial cell cultures were subsequently exposed to DEP of varying organic carbon composition, and the resulting cytotoxic (LDH), antioxidant (GSH), and cytoprotective (HO-l) responses of the cell cultures evaluated. We observed that whereas healthy MTE cells were seemingly unaffected by DEP exposure, healthy LA-4 cells exposed to organic carbon-rich particles induced adaptive anti-oxidant (GSH) and cytoprotective (HO-l) responses with no apparent change in cell injury (LDH). However, inflamed LA-4 cells exposed to particles rich in organic carbon resulted in oxidative stress culminating in increased cell injury. Similarly, inflamed MTE cells exposed to organic carbon-rich DEP resulted in the dysfunction of the epithelial barrier. Thus, epithelial cells stressed by a state ofinflammation and then exposed to organic rich DEP appear unable to respond to the additional oxidative stress, resulting in enhanced cell injury. The adverse health outcomes associated with exposure to traffic-related air pollutants, like DEP, in asthmatic patients may be due, at least in part, to similar mechanisms.
