Bronchial hyperresponsiveness, epithelial damage, and airway eosinophilia after single and repeated allergen exposure in a rat model of anhydride‐induced asthma

• Published in: Allergy (Copenhagen) Vol. 52; no. 7; pp. 739 - 746
• Main Authors: Cui, Z.‐H., Sjöstrand, M., Pullerits, T., Andius, P., Skoogh, B.‐E., Lötvall, J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.1997; Blackwell
• Subjects: Animals; Biological and medical sciences; Bronchi - immunology; Bronchi - pathology; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - pathology; bronchial hyperresponsiveness; Bronchial Provocation Tests; eosinophilia; Eosinophilia - immunology; epithelial damage; Epithelium - pathology; Experimental and animal immunopathology. Animal models; Humans; Immunoglobulin E - analysis; Immunoglobulin G - analysis; Immunopathology; Male; Medical sciences; Phthalic Anhydrides - administration & dosage; Phthalic Anhydrides - immunology; Rats; Rats, Inbred BN; Respiratory Hypersensitivity - immunology; Respiratory Hypersensitivity - pathology; trimellitic anhydride; Vaccination; Immunopathology; Allergy; Animal model; Hyperreactivity; Rat; Respiratory disease; Toxicity; Rodentia; Granulocyte; Bronchus; Organic anhydride; Epithelium; Eosinophil; Asthma; Vertebrata; Mammalia; Animal; Obstructive pulmonary disease; Lesion; Provocation test
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/j.1398-9995.1997.tb01231.x

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 < 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.