Journal Article

Differential Potentiation of Allergic Lung Disease in Mice Exposed to Chemically Distinct Diesel Samples

Tina Stevens, Seung-Hyun Cho, William P. Linak and M. Ian Gilmour

in Toxicological Sciences

Volume 107, issue 2, pages 522-534
Published in print February 2009 | ISSN: 1096-6080
Published online December 2008 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfn248
Differential Potentiation of Allergic Lung Disease in Mice Exposed to Chemically Distinct Diesel Samples

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Numerous studies have demonstrated that diesel exhaust particles (DEP) potentiate allergic immune responses, however the chemical components associated with this effect, and the underlying mechanisms are not well understood. This study characterized the composition of three chemically distinct DEP samples (N, C, and A-DEP), and compared post-sensitization and post-challenge inflammatory allergic phenotypes in BALB/c mice. Mice were instilled intranasally with saline or 150 μg of N-DEP, A-DEP, or C-DEP with or without 20 μg of ovalbumin (OVA) on days 0 and 13, and were subsequently challenged with 20 μg of OVA on days 23, 26, and 29. Mice were necropsied 18 h post-sensitization and 18 and 48 h post-challenge. N-DEP, A-DEP, and C-DEP contained 1.5, 68.6, and 18.9% extractable organic material (EOM) and 47, 431, and 522 μg of polycyclic aromatic hydrocarbons (PAHs), respectively. The post-challenge results showed that DEP given with OVA induced a gradation of adjuvancy as follows: C-DEP ≈ A-DEP > N-DEP. The C- and A-DEP/OVA exposure groups had significant increases in eosinophils, OVA-specific IgG1, and airway hyperresponsiveness. In addition, the C-DEP/OVA exposure increased the T helper 2 (TH2) chemoattractant chemokine, thymus and activation-regulated chemokine and exhibited the most severe perivascular inflammation in the lung, whereas A-DEP/OVA increased interleukin (IL)-5 and IL-10. In contrast, N-DEP/OVA exposure only increased OVA-specific IgG1 post-challenge. Analysis of early signaling showed that C-DEP induced a greater number of TH2 cytokines compared with A-DEP and N-DEP. The results suggest that potentiation of allergic immune responses by DEP is associated with PAH content rather than the total amount of EOM.

Keywords: diesel exhaust articles; adjuvancy; airway inflammation; allergy; mice

Journal Article.  8907 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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