Resistance of very young mice to inhaled allergen sensitization is overcome by coexposure to an air-pollutant aerosol

The role of air pollution in the initiation of asthma is controversial. We sought to model the potential effects of air pollution on immune responses to inhaled allergens in developing lungs by using very young mice. Neonatal mice were repeatedly exposed to aerosolized ovalbumin (OVA; 3% in phosphat e-buffered saline for 10 min/d, from Days 5 to 15 of age). Some mice were a lso exposed to leachate of residual oil fly ash (ROFA-s), a surrogate for a mbient air particles, for 30 min, on Days 6, 8, and 10 of age). Repeated ex posure of very young mice to allergen alone (OVA) or pollutant alone (ROFA- s) had no effect on airway hyperresponsiveness (AHR, measured as enhanced p ause (Penh) with noninvasive plethysmography at Day 16 of age), and did not cause inflammation or OVA-specific antibody production. Similar exposures of adult mice to either OVA alone or to OVA + ROFA-s did result in AHR, wit hout evidence of enhancement by combined exposure. In contrast, very young mice exposed to both OVA and ROFA-s showed significantly increased AHR (e.g ., Penh with 50 mg/ml methacholine for OVA + ROFA-s versus OVA alone = 2.6 +/- 0.4 [mean +/- SE], versus 1.2 +/- 0.1; p < 0.01, n greater than or equa l to 15), and produced OVA-specific IgE and IgG upon allergen challenge a w eek later. Immunostaining of airways taken from mice at Day 11 showed a mar ked increase in la(+) cells after OVA + ROFA-s exposure. We conclude that e xposure to pollutant aerosols can disrupt normal resistance to sensitizatio n to inhaled allergens, and can thereby promote development of airway hyper sensitivity in this neonatal/juvenile mouse model.