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Comparisons of the pro-oxidant and proinflammatory effects of organic diesel exhaust particle chemicals in bronchial epithelial cells and macrophages

Division of Clinical Immunology and Allergy, Department of Medicine, University of California-Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
The Journal of Immunology (Impact Factor: 5.36). 11/2002; 169(8):4531-41. DOI: 10.4049/jimmunol.169.8.4531
Source: PubMed

ABSTRACT Inhaled diesel exhaust particles (DEP) exert proinflammatory effects in the respiratory tract. This effect is related to the particle content of redox cycling chemicals and is involved in the adjuvant effects of DEP in atopic sensitization. We demonstrate that organic chemicals extracted from DEP induce oxidative stress in normal and transformed bronchial epithelial cells, leading to the expression of heme oxygenase 1, activation of the c-Jun N-terminal kinase cascade, IL-8 production, as well as induction of cytotoxicity. Among these effects, heme oxygenase 1 expression is the most sensitive marker for oxidative stress, while c-Jun N-terminal kinase activation and induction of apoptosis-necrosis require incremental amounts of the organic chemicals and increased levels of oxidative stress. While a macrophage cell line (THP-1) responded in similar fashion, epithelial cells produced more superoxide radicals and were more susceptible to cytotoxic effects than macrophages. Cytotoxicity is the result of mitochondrial damage, which manifests as ultramicroscopic changes in organelle morphology, a decrease in the mitochondrial membrane potential, superoxide production, and ATP depletion. Epithelial cells also differ from macrophages in not being protected by a thiol antioxidant, N-acetylcysteine, which effectively protects macrophages against cytotoxic DEP chemicals. These findings show that epithelial cells exhibit a hierarchical oxidative stress response that differs from that of macrophages by more rapid transition from cytoprotective to cytotoxic responses. Moreover, epithelial cells are not able to convert N-acetylcysteine to cytoprotective glutathione.

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    • "After the particles or pathogens have eluded or overwhelmed the epithelial barrier of the upper airways, they come into contact with the dedicated antigen presenting dendritic cells (DCs) (e.g. Steinman and Cohn, 1973; Nicod, 1997; Lipscomb and Masten, 2002; Holt, 2005) which are highly phagocytic (Dreher et al., 2001; Kiama et al., 2001, 2006; Walter et al., 2001). If they reach the alveolar surface, they are dealt with by the PSMs (e.g. "
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    • "While activation of p38 MAPK was analyzed 2 and 4 h after the addition of OE, COX-2 protein was determined at the 16-h time point [16] [21] [27]. Cell lysate preparation, protein assay and western blot were performed as previously described [15] [27] [28]. HO-1, phosphorylated p38, total p38, COX- 2, and ␤-actin proteins were detected using respective primary Abs (1:1000) followed by horseradish peroxidaseconjugated secondary Abs (1:1000). "
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