title: Bronchial hyperresponsiveness, epithelial damage, and airway eosinophilia after single and repeated allergen exposure in a rat model of anhydride-induced asthma.
abstract: Bronchial hyperresponsiveness (BHR) and damage of the epithelium, as well as eosinophilia in the airway wall, induced by trimellitic anhydride (TMA) in sensitized brown Norway rats were studied. Rats were challenged once or seven times with aerosol of TMA conjugated to rat serum albumin (TMA-RSA) 3 weeks after intradermal TMA sensitization. Airway responsiveness (-log PC300 of acetylcholine i.v.) was measured 24 h after allergen challenge. Epithelial lesion and eosinophil infiltration in the airway walls were quantified under light microscopy, and TMA-specific IgE and IgG in serum were evaluated with ELISA. High levels of TMA-specific IgE and IgG were found in all rats in the sensitized groups compared to nonsensitized groups (P < 0.001). Repeated allergen challenges of 0.03% TMA-RSA for 7 consecutive days enhanced the level of TMA-specific IgG, compared to single challenge (P < or = 0.05). Single allergen challenge of 0.3% TMA-RSA had a nonsignificant tendency to produce BHR in sensitized rats compared to nonsensitized rats (P = 0.06). However, repeated allergen challenges (0.003% and 0.03% TMA-RSA for 7 consecutive days) produced significant BHR in sensitized rats (P < 0.05). Furthermore, repeated low-dose (0.003%) TMA-RSA challenge produced more BHR than a 10 times higher single dose (0.03%) (P < 0.05). Slight damage of the airway epithelium was seen in sensitized and repeat-challenged groups. However, bronchial eosinophilia was found in the sensitized and single-challenged groups, but not in nonsensitized nonchallenged, and sensitized repeat-challenged groups (P < 0.005). We conclude that the brown Norway rat can be sensitized with TMA, and that repeated low-dose allergen challenges produce slight epithelial damage and BHR which is independent of ongoing eosinophilia in the airway wall.
authors.affiliation: Department of Clinical Pharmacology, Göteborg University, Sweden.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Cui
authors.forename: M
authors.initials: M
authors.lastname: Sjöstrand
authors.forename: T
authors.initials: T
authors.lastname: Pullerits
authors.forename: P
authors.initials: P
authors.lastname: Andius
authors.forename: B E
authors.initials: BE
authors.lastname: Skoogh
authors.forename: J
authors.initials: J
authors.lastname: Lötvall
mesh_terms: D000818:Animals; D001980:Bronchi / Q000276:immunology / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000473:pathology; D001985:Bronchial Provocation Tests; D004802:Eosinophilia / Q000276:immunology*; D004848:Epithelium / Q000473:pathology; D006801:Humans; D007073:Immunoglobulin E / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D010796:Phthalic Anhydrides / Q000008:administration & dosage / Q000276:immunology*; D051381:Rats; D011914:Rats, Inbred BN; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology; D014611:Vaccination
chemical_list: D007074:Immunoglobulin G; D010796:Phthalic Anhydrides; D007073:Immunoglobulin E; C015559:trimellitic anhydride