Resistance of Very Young Mice to Inhaled Allergen Sensitization Is Overcome by Coexposure to an Air-Pollutant Aerosol

Abstract

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 phosphate-buffered saline for 10 min/d, from Days 5 to 15 of age). Some mice were also exposed to leachate of residual oil fly ash (ROFA-s), a surrogate for ambient air particles, for 30 min, on Days 6, 8, and 10 of age). Repeated exposure of very young mice to allergen alone (OVA) or pollutant alone (ROFA-s) had no effect on airway hyperresponsiveness (AHR, measured as enhanced pause (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, without 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 >/= 15), and produced OVA-specific IgE and IgG upon allergen challenge a week later. Immunostaining of airways taken from mice at Day 11 showed a marked increase in Ia(+) cells after OVA + ROFA-s exposure. We conclude that exposure to pollutant aerosols can disrupt normal resistance to sensitization to inhaled allergens, and can thereby promote development of airway hypersensitivity in this neonatal/juvenile mouse model.

Severe Vitamin E deficiency modulates airway allergic inflammatory responses in the murine asthma model

“…For the three response variables, there were no significant differences between the two genotypes. The normal lung lavage from a healthy mouse contains more that 90% alveolar macrophages [34] and our observations in the airexposed groups were consistent with this finding. The increase in inflammatory cells seen in the BAL from the OVA-exposed groups is predominantly accounted for by the increase in lung lavage eosinophils.…”

Air pollutant-enhanced respiratory disease in experimental animals.

“…These challenges are not antigenic in nature but rather behave as irritants in provoking inflammation and/or bronchoconstriction. Similar effects have been seen in allergic animals exposed to ROFA as illustrated here and in previous reports (27,28). This general increase in airway responsiveness and lung injury through dual exposure to allergen and PM may be an additive effect of two proinflammatory stimuli, although synergistic relationships in which both stimuli are required to elicit a pulmonary response are also possible.…”

Allergen-Independent Maternal Transmission of Asthma Susceptibility

“…Our strategy was to use an intentionally suboptimal protocol in which only a single i.p. injection was used for sensitization, rather than the two injections that consistently give robust AHR and AI when animals are subsequently challenged with aerosolized allergen (19,20). After observing increased susceptibility in this basic model, we investigated whether or not the maternal effect is allergen specific by challenge of baby mice with a second, unrelated allergen, casein (Cs).…”