Increased airway hyperresponsiveness and inflammation in a juvenile mouse model of asthma exposed to air-pollutant aerosol.
Asthma and its exacerbation by air pollution are major public health problems. This investigation sought to more precisely model this disorder, which primarily affects children, by using very young mice. The study first attempted to create allergic airway hypersensitivity in neonatal mice and to determine if physiologic testing of airway function was possible in these small animals. Neonatal mice were sensitized by i.p. injection of ovalbumin (OVA, 5 microg) and alum (1 mg) at 3 and 7 d of age. One week later, mice were challenged by allergen nebulization (3% OVA in PBS, 10 min/d, d 14-16). OVA-exposed mice showed: (1) increased airway hyperresponsiveness (AHR) to methacholine by whole-body plethysmography; (2) eosinophilia in bronchoalveolar lavage (BAL) fluid; (3) airway inflammation using histopathology techniques; and (4) elevated serum anti-OVA immunoglobulin E. Hence, these neonatal mice were successfully sensitized and manifested "asthmatic" responses after allergen challenge. Experiments were conducted to investigate the effect of one surrogate for ambient air particles, residual oil fly ash (ROFA), on this juvenile asthma model. Aerosolized ROFA leachate (supernatant of 50 mg/ml, 30 min, on d 15) had no marked effect alone, but caused a significant increase in AHR and airway inflammation in OVA-sensitized and challenged mice. This synergistic effect was abrogated by the antioxidant dimethylthiourea (DMTU, 3 mg/kg mouse, i.p.). This model may be useful to study air pollution-mediated exacerbation of asthma in children.
Hamada
K
K
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Goldsmith
C A
CA
Kobzik
L
L
D000336:Aerosols; D000393:Air Pollutants / Q000633:toxicity*; D000485:Allergens / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D001991:Bronchitis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D002244:Carbon / Q000633:toxicity; D060729:Coal Ash; D004797:Enzyme-Linked Immunosorbent Assay; D016166:Free Radical Scavengers / Q000494:pharmacology; D007073:Immunoglobulin E / Q000032:analysis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology / Q000633:toxicity; D052638:Particulate Matter; D010641:Phenotype; D010991:Plethysmography; D015842:Serine Proteinase Inhibitors / Q000276:immunology / Q000633:toxicity; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D000336:Aerosols; D000393:Air Pollutants; D000485:Allergens; D060729:Coal Ash; D016166:Free Radical Scavengers; D052638:Particulate Matter; D015842:Serine Proteinase Inhibitors; D007073:Immunoglobulin E; D002244:Carbon; C038983:1,3-dimethylthiourea; D010047:Ovalbumin; D013890:Thiourea