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 Ambient 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 microl, 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 microl, 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 bronchoalveolar 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.

A rapid assessment of the impact of hazard reduction burning around Sydney, May 2016

“…Co-exposures to aeroallergens (such as grass pollen) and particles result in synergistic effects that lead to much stronger allergic responses in experimental animals and human beings than the sum of the responses to each of these constituents (D'Amato et al, 2005;Steerenberg et al, 2003;Diaz-Sanchez et al, 1999). However, this is different from studies in which the effects of particles have been studied on already allergic subjects.…”

The Adjuvant Effect of Ambient Particulate Matter Is Closely Reflected by the Particulate Oxidant Potential

“…PM adjuvant effects have been demonstrated in both animal and human studies (Diaz-Sanchez et al 1997;Gilliland et al 2004;Kleinman et al 2007;Matsumoto et al 2006;Steerenberg et al 2003aSteerenberg et al , 2003bStevens et al 2008;Whitekus et al 2002). Although in humans it has been shown that intranasal instillation of diesel exhaust particles (DEP) could enhance ragweed-induced immunoglobulin E (IgE) and interleukin-4 (IL-4) production, results from animal studies have demonstrated that low-dose challenge by aerosolized inhalation or intratracheal instillation could enhance allergic sensitization to an experimental allergen such as ovalbumin (OVA) (Diaz-Sanchez et al 1997;Gilliland et al 2004;Matsumoto et al 2006;Steerenberg et al 2003aSteerenberg et al , 2003bStevens et al 2008;Whitekus et al 2002).…”

“…This hypothesis has not yet been formally tested in an in vivo model for PM adjuvant effects. In fact, most of the animal studies to date have used poorly calculated PM doses that far exceed the real-life exposure amounts and do not address the mechanism of the adjuvant effect (Ichinose et al 2004;Inoue et al 2005;Steerenberg et al 2003aSteerenberg et al , 2003b. Thus, we aimed to determine whether there is a positive correlation between the adjuvant effect of ambient concentrated PM and their content of redox cycling organic chemicals.…”

“…Although in humans it has been shown that intranasal instillation of diesel exhaust particles (DEP) could enhance ragweed-induced immunoglobulin E (IgE) and interleukin-4 (IL-4) production, results from animal studies have demonstrated that low-dose challenge by aerosolized inhalation or intratracheal instillation could enhance allergic sensitization to an experimental allergen such as ovalbumin (OVA) (Diaz-Sanchez et al 1997;Gilliland et al 2004;Matsumoto et al 2006;Steerenberg et al 2003aSteerenberg et al , 2003bStevens et al 2008;Whitekus et al 2002). Similar findings in studies using ambient PM exposure, including the recent Los Angeles study, have demonstrated that the inhalation of concentrated ambient PM near a busy freeway could increase antigen-induced airway responses in mice (Kleinman et al 2007).…”

Effects of a Diphtheria-Tetanus-Acellular Pertussis Vaccine on Immune Responses in Murine Local Lymph Node and Lung Allergy Models

“…The second allergy model is a lung allergy model with intranasal sensitization and challenge with ovalbumin (OVA). Whereas OVA alone induced OVA-specific IgE, lung pathology, and eosinophils in the BALF, coexposure of OVA and particulate matter (diesel exhaust particles, residual oil fly ash, and ambient particles) during the sensitization phase increased the size of these effects (33). Moreover, it has been described as a model for human lung allergy (14).…”