TIMING OF LOW-LEVEL NO2 EXPOSURE ALTERS ANTIGEN-SPECIFIC IgE, IgG1, AND IgG2a ANTIBODY PRODUCTION IN MICE

Abstract

Epidemiological evidence suggests that air pollutants may increase the prevalence of bronchial hyperresponsiveness and exacerbate the asthma. However, the role of the ambient level of NO2 in the induction of allergic disease is still unclear. In this study, we investigated whether exposure of mice to low concentrations of NO2 before or after sensitization with ovalbumin (OVA) enhances an antigen-specific immune response. Sensitization of mice with an aerosol of OVA at 3-wk intervals after initiation of 2 ppm NO2 exposure resulted in suppression of OVA-specific immunoglobulin (Ig)E, IgG1, and IgG2a antibody production in plasma. OVA-specific IgG1 and IgG2a antibody production was also significantly decreased in the bronchoalveolar lavage (BAL) fluid of exposed mice. In contrast, when mice were exposed to NO2 after intraperitoneal immunization with OVA and sensitization with OVA aerosol at 3-wk intervals during NO2 exposure, OVA-specific IgE antibody production in the plasma of mice exposed to 0.5 and 1.0 ppm NO2 was significantly increased when compared with control mice. Moreover, antigen-specific IgG1 and IgG2a antibody production in the plasma of exposed mice showed a trend to be increased, but not significantly. OVA-specific IgG1 and IgG2a antibody production was significantly increased in the BAL fluid of mice exposed to 1 ppm NO2 and 2 ppm NO2, respectively. To assess the factors modulating antibody production in the NO2-exposed mice before or after immunization with OVA, the local level of cytokine in BAL fluid was measured using an enzyme-linked immunosorbent assay (ELISA). In the BAL fluid of mice exposed to NO2 after immunization there were no differences in interleukin-4 (IL-4) and IL-10 levels, while IL-12 production showed a significant decrease. Although IL-10 in the BAL fluid of mice exposed to 2.0 ppm NO2 before immunization was increased significantly, IL-4 levels showed significant decreases in mice exposed to 1.0 and 2.0 ppm NO2. These results suggest that ambient levels of NO2 increase antibody production in mice preimmunized with antigen, but not in mice without preimmunization.