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DIESEL EXHAUST PARTICLE COMPOSITION AND THE METHOD OF SONICATION INFLUENCE THE ADJUVANCY EFFECT AND TARC PRODUCTION
Citation:
STEVENS, T., M. J. DANIELS, E. BOYKIN, AND M. I. GILMOUR. DIESEL EXHAUST PARTICLE COMPOSITION AND THE METHOD OF SONICATION INFLUENCE THE ADJUVANCY EFFECT AND TARC PRODUCTION. Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.
Description:
Numerous reports have shown diesel exhaust particles (DEP) can act as an immunological adjuvant in asthma. Recent interest has focused on thymus and activation-regulated chemokine (TARC) as an important modulator of this effect. This study evaluated the adjuvancy effects of three chemically different DEP prepared by two different sonication methods and measured TARC production for all conditions. The samples were NIST SRM 2975 (NDEP) generated from a heavy forklift, an automobile generated DEP (ADEP), and DEP (CDEP) generated from a diesel engine used to power a compressor. These samples differed in the percentage of extractable organic material; NDEP, ADEP, and CDEP contained 1.5%, 67%, and 18.9%, respectively. Samples were sonicated in a waterbath for 40 min or with a point sonicator for 10 min. BALB/C mice were instilled intranasally with saline or 150 ug of NDEP, ADEP, or CDEP with 20 ug of ovalbumin on days 0 and 13, and then challenged with ovalbumin on days 23, 26, and 29. Immune and inflammatory endpoints in the lung were assessed 18 and 48 hrs after the last challenge. With the waterbath sonicated samples, mice exposed to NDEP had significantly higher neutrophil infiltration and IL4, IL5, and IL13 cytokine production in the BAL fluid after 18 hrs relative to ovalbumin alone. By 48 hrs, these mice had the highest levels of eosinophils and lung injury compared to all groups. However, exposure to point sonicated ADEP or CDEP caused greater adjuvancy than NDEP for these same indicators of allergic lung disease. In addition, airway hyperactivity was measured and found to be highest in the ADEP exposed mice. Analysis of TARC showed that this chemokine was associated with the strongest adjuvant effect depending on the preparation technique. These results show that source and composition as well as methods of sonication are important in regulating the extent of adjuvancy, and that these effects are associated with the presence of the Th2 chemokine, TARC. (This abstract does not reflect EPA policy)