ToxSci Advance Access originally published online on December 12, 2008
Toxicological Sciences 2009 107(2):522-534; doi:10.1093/toxsci/kfn248
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Published by Oxford University Press 2008.
Differential Potentiation of Allergic Lung Disease in Mice Exposed to Chemically Distinct Diesel Samples
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* Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599
Air Pollution and Prevention Control Division, National Risk Management Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Research Participation Program, Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee 37831
Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Research Triangle Park, North Carolina 27711
1 To whom correspondence should be addressed at U.S. Environmental Protection Agency, Research Triangle Park, NC 27711. Fax: (919) 541-0026. E-mail: gilmour.ian{at}epa.gov.
Received June 6, 2008; accepted November 25, 2008
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Abstract |
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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.
Key Words: diesel exhaust articles; adjuvancy; airway inflammation; allergy; mice.