Inflammatory responses in skin and airways after allergen challenge in brown Norway rats sensitized to trimellitic anhydride.
Trimellitic anhydride (TMA) is a low-molecular-weight compound which causes occupational allergy. Brown Norway rats were sensitized to TMA injected intradermally (0.3% TMA suspended in oil). Three weeks later, we examined responses to either free TMA injected intradermally, or TMA conjugated to rat serum albumin (TMA-RSA) given by inhalation (0.5%, nebulized for 15 min). Twenty-one days after the sensitization, Evans blue dye was given i.v. (20 mg/kg), and extravasation of dye in skin was measured 30 min after oil or TMA injections (0.03-10% in oil). In a separate series of experiments, we evaluated the accumulation of eosinophils in the skin after single and repeated injections of TMA (0.03-0.3%). The injection sites were removed and fixed in formalin 18-24 h after the last injection. In a third series of experiments, we evaluated the effects of airway exposure to TMA-RSA (0.5% in 0.9% saline) on the accumulation of eosinophils in the bronchial wall counted with quantitative light microscopy. Intradermal injections of free TMA caused a dose-dependent increase of Evans blue dye extravasation which was significantly higher in sensitized animals than in controls. Skin histology revealed a significant and dose-dependent increase in eosinophils after repeated TMA injections in sensitized animals. Exposure to aerosolized TMA-RSA caused a significant increase of eosinophils in the bronchial wall of sensitized rats compared with nonsensitized rats. Sensitized animals showed significantly higher levels of specific IgG and IgE. We conclude that brown Norway rats can be used as a model of TMA-induced allergic inflammation, mimicking occupational asthma.
Andius
P
P
Division of Clinical Pharmacology, Göteborg University, Gothenborg, Sweden.
Arakawa
H
H
Mölne
J
J
Pullerits
T
T
Skoogh
B E
BE
Lötvall
J
J
D000279:Administration, Cutaneous; D000280:Administration, Inhalation; D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000097:blood / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004804:Eosinophils; D005260:Female; D007073:Immunoglobulin E / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007958:Leukocyte Count; D009784:Occupational Diseases / Q000276:immunology*; D010796:Phthalic Anhydrides / Q000008:administration & dosage / Q000276:immunology*; D051381:Rats; D011914:Rats, Inbred BN; D012130:Respiratory Hypersensitivity / Q000097:blood / Q000276:immunology*; D012867:Skin / Q000166:cytology / Q000276:immunology
D007074:Immunoglobulin G; D010796:Phthalic Anhydrides; D007073:Immunoglobulin E; C015559:trimellitic anhydride