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  • Title: Differential potentiation of allergic lung disease in mice exposed to chemically distinct diesel samples.
    Author: Stevens T, Cho SH, Linak WP, Gilmour MI.
    Journal: Toxicol Sci; 2009 Feb; 107(2):522-34. PubMed ID: 19074765.
    Abstract:
    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 microg of N-DEP, A-DEP, or C-DEP with or without 20 microg of ovalbumin (OVA) on days 0 and 13, and were subsequently challenged with 20 microg 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 microg 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 approximately 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 (T(H)2) 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 T(H)2 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.
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