Optimization of Route of Administration for Coexposure to Ovalbumin and Particle Matter to Induce Adjuvant Activity in Respiratory Allergy in the Mouse

Abstract

Epidemiological and experimental studies have not only shown that air pollution induces increased pulmonary morbidity, and mortality, but also that air pollution components may potentiate allergic responses. The respiratory allergy model to ovalbumin in the mouse has been shown a useful tool to characterize the adjuvant potency of air pollution components. However, the choice for the most effective route of administration for testing small amounts of air pollution component is hampered by the diversity of routes of administration used. To test the adjuvant activity of airborne particles (Ottawa dust EHC-93), we studied the optimal route of respiratory administration: intranasally (in) and aerosol (aero) in comparison with responses observed by intraperitoneal (ip) with diesel exhaust particles (DEP) as a positive control. Our results show that the combination of in/aero with ovalbumin caused almost similar immunoglobulin (Ig)E and inflammatory responses compared to the ip/aero. In/in application induced less responses for IgE, less inflammation in the lung, and less increased numbers of eosinophils in the bronchoalveolar lavage (BAL). This response increased dramatically when ovalbumin was coadministered with DEP. Subsequently, EHC-93, which is made up of airborne particles, was tested via the in/in route of administration. EHC-93 induced similar IgE responses, inflammation, and eosinophilic response in BAL compared to DEP. In addition, EHC-93 increased the airway responsiveness of the ovalbumin-sensitized mice measured in unrestrained condition and not in nonsensitized control mice. It is concluded that intranasal sensitization with intranasal challenge with airborne particles (EHC-93) is an effective route of administration to show potency of adjuvant activity of airborne particles.

Sensitivity to Ozone, Diesel Exhaust Particles, and Standardized Ambient Particulate Matter in Rats with aListeria Monocytogenes-Induced Respiratory Infection

“…However, the inhibitory activity of the Th1 regulatory system is less obvious. Exposure to ozone suppressed ovalbumin-induced IgG2a in sensitized mice (Neuhaus-Steinmetz et al, 2000), but exposure to EHC-93 in this animal model increased the levels of ovalbumin-specific IgE, IgG1, and IgG2a (Steerenberg et al, 2003a(Steerenberg et al, , 2003b. It has also been shown that ozone downregulates the IgG2a response in an animal model for respiratory infection (van Loveren et al, , 1988Steerenberg et al, 1996;Cohen et al, 2002).…”

Co-Delivery of Ovalbumin and CpG Motifs into Microparticles Protected Sensitized Mice from Anaphylaxis

“…The design of this experiment was modified from previous reports [19, 20]. Briefly, BALB/c mice (n = 7–8) were sensitized twice intraperitoneally with 50 µg OVA adsorbed in 2 mg of Alum on days 0 and 7 (fig.…”

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).…”