Mixed air pollution: ambient particles, acid aerosols, NO2 and ozone in development and aggravation of the allergic response

The project hypothesis: When put on the mucosa of the airways, fine ambient air particles need a co-factor causing inflammation to fully express their potential to exert a strong adjuvant effect on the allergic immune response and allergic inflammation. T he project hypothsis is based on two observations. One is the general observation that in real life, exposure to fine particles will occur in the context of acid aerosols, NO2 and ozone. The second is our observation in the EU-funded RAIAP project. Wherea s fine particles when injected subcutaneously have a strong adjuvant effect on the allergen-specific IgE response even at low doses, this strong adjuvant effect becomes manifest only if the particle dose is high enough to cause inflammation if particles a nd allergen are deposited on the nasal mucosa.- In epidemiological studies on acute worsening of asthma because of pollution, the strongest effect in a number of studies has been found to be associated with fine rather than coarse particles. It is of cons iderable interest to find out if inflammatory co-factors are needed for fine particles to exert their adverse health effects. We address this question in an intranasal immunization model in the mouse, in which the mice will be exposed to the allergen oval bumin and fine particles, with or without concomitant exposure to slightly irritating acid aerosol/acid buffer, NO2 or ozone. We will use both particles collected from ambient air, and polystyrene model particles of similar size. Main outcome parameters will be the specific IgE, IgG1 and IgG2a antibody primary as well as secondary response to ovalbumin, and inflammatory markers in bronchial lavage fluid and airway mucosa-draining lymph nodes. Determine relevant gene expression by Affymetrix. The post-do ctoral project represents a collaborative effort between Folkehelseinstituttet in Oslo (study base) and Institute for Cancer Research and Molecular medicine, NTNU, Trondheim (inalation studies and Affymetrix)