Adjuvant Activity of Various Diesel Exhaust and Ambient Particles in Two Allergic Models

Abstract

In the framework of an EU study entitled "Respiratory Allergy and Inflammation Due to Ambi-ent Particles" (RAIAP), various collected particulate matter samples were to be tested for their adjuvant potency in two animal models of allergy. A pollen allergy model in the Brown Norway (BN) rat and an ovalbumin model in the BALB/c mouse were used in this study to compare the discriminatory value of these two models and to evaluate them for later studies of collected RAIAP-samples. Two different sources of diesel exhaust particles (DEP I and DEP II ), a residual oil fly ash source (ROFA), and two sources of ambient particles (Ottawa dust, EHC-93, and road tunnel dust, RTD) were tested. Rats were sensitized intratracheally with Timothy grass pollen (Phleum pratense, 200 µl, 10 mg/ml) on d 0, challenged on d 21, and examined on d 25. Mice were sensitized intranasally at d 0 and 14, challenged intranasally at d 35, 38, and 41 (50 µl, 0.4 mg ovalbumin/ml), and examined at d 42. Particulate matter (PM) was administered either during the sensitization phase only or during the sensitization and challenge phases (for mice only) or during the challenge phase only. In the pollen model, only DEP I , but not DEP II , ROFA, EHC-93, and RTD, stimulated the immunoglobulin (Ig) E and IgG1 response in serum to pollen allergens. In addition to this adjuvant effect noted, no other biomarkers in lung or bronchoalve-olar lavage (BAL) revealed adjuvant activity in the pollen model. In the BAL of BN rats exposed to a combination of pollen and PM, the percentages of eosinophilic granulocytes were decreased compared to the BAL of BN rats immunized with pollen only. In the ovalbumin model, the IgE levels in serum were increased in mice after coexposure to ovalbumin and PM (including DEPI , DEPII , ROFA, EHC-93, and RTD) in the sensitization phase but not after coexposure during the challenge phase only. The inflammatory response was greater in the lung, predominantly the influx of eosinophilic granulocytes, as was observed by both histopathological examination and BAL analysis. In addition, BAL levels of inflammatory interleukin (IL)-4 were increased. Based on the IgE antibody response to ovalbumin, the ovalbumin model ranked the adjuvant capacity of the particles in the following order: RTD > ROFA > EHC-93 > DEPI > DEPII . In conclusion, the ovalbumin model is a sensitive system to detect adjuvant activity of airborne particles, whereas the pollen-induced allergy model in rat was less sensitive.