title: Susceptibility of inflamed alveolar and airway epithelial cells to injury induced by diesel exhaust particles of varying organic carbon content.
abstract: 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 novel in vitro system to model both the healthy and inflamed lung, the susceptibility of epithelial cells exposed to DEP of varying organic carbon content 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 (tumor necrosis factor [TNF] alpha + interleukin [IL]-1 beta + interferon [IFN] gamma) to model a mild inflammatory state. Epithelial cells were subsequently exposed to DEP of varying organic carbon content, and the resultant cytotoxic, cytoprotective, or antioxidant cell responses were inferred by changes in lactate dehydrogenase (LDH) release, heme oxygenase-1 (HO-1) expression, or glutathione levels, respectively. Data showed that exposure of healthy LA-4 cells to organic carbon-rich DEP (25 microg/cm(2); 24 h) induced adaptive cytoprotective/antioxidant responses with no apparent cell injury. In contrast, exposure of inflamed LA-4 cells resulted in oxidative stress culminating in significant cytotoxicity. Exposure of healthy MTE cells to organic carbon-rich DEP (20 microg/cm(2); 24 h) was seemingly without effect, whereas exposure of inflamed MTE cells resulted in increased epithelial solute permeability. Thus, surface lung epithelial cells stressed by a state of inflammation and then exposed to organic carbon-rich DEP appear unable to respond to the additional oxidative stress, resulting in epithelial barrier dysfunction and injury. Adverse health outcomes associated with exposure to traffic-related air pollutants, like DEP, in patients with preexisting inflammatory respiratory diseases may be due, in part, to similar mechanisms.
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Manzo
authors.forename: Ralph
authors.initials: R
authors.lastname: Slade
authors.forename: Judy H
authors.initials: JH
authors.lastname: Richards
authors.forename: John K
authors.initials: JK
authors.lastname: McGee
authors.forename: Linda D
authors.initials: LD
authors.lastname: Martin
authors.forename: Janice A
authors.initials: JA
authors.lastname: Dye
mesh_terms: D000199:Actins / Q000378:metabolism; D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D002244:Carbon / Q000633:toxicity*; D002478:Cells, Cultured; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000187:drug effects*; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects*; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000199:Actins; D000393:Air Pollutants; D052638:Particulate Matter; D001335:Vehicle Emissions; D002244:Carbon; D007770:L-Lactate Dehydrogenase; D051547:Heme Oxygenase-1; D005978:Glutathione