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

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.

[1]  S. Oddera,et al.  Airway eosinophilic inflammation, epithelial damage, and bronchial hyperresponsiveness in patients with mild‐moderate, stable asthma , 1996, Allergy.

[2]  J. Solway,et al.  Persistent airway hyperresponsiveness and histologic alterations after chronic antigen challenge in cats. , 1995, American journal of respiratory and critical care medicine.

[3]  S. V. Von Essen,et al.  Airway epithelial cells: functional roles in airway disease. , 1994, American journal of respiratory and critical care medicine.

[4]  K. Chung,et al.  Effects of prolonged repeated exposure to ovalbumin in sensitized brown Norway rats. , 1994, American journal of respiratory and critical care medicine.

[5]  J. Lötvall,et al.  Role of eicosanoids in airflow obstruction and airway plasma exudation induced by trimellitic anhydride‐conjugate in guinea‐pigs 3 and 8 weeks after sensitization , 1994, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[6]  L. Grammer,et al.  Immunologic cross-reactivity of acid anhydrides with immunoglobulin E against trimellityl-human serum albumin. , 1994, The Journal of laboratory and clinical medicine.

[7]  J. P. Hayes,et al.  Airway allergy to trimellitic anhydride in guinea pigs: different time courses of IgG1 titer and airway responses to allergen challenge. , 1993, The Journal of allergy and clinical immunology.

[8]  D. Hyde,et al.  Effects of ozone and neutrophils on function and morphology of the isolated rat lung. , 1993, The American review of respiratory disease.

[9]  O. Zetterstrom,et al.  Increase in non‐specific bronchial responsiveness after repeated inhalation of low doses of allergen , 1993, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[10]  F. Mitsunobu,et al.  Airway inflammation and bronchial hyperresponsiveness in patients with asthma. Comparison between atopic and nonatopic asthma. , 1993, Arerugi = [Allergy].

[11]  A. Kuroiwa,et al.  Guinea pig model of immunologic asthma induced by inhalation of trimellitic anhydride. , 1992, The American review of respiratory disease.

[12]  K. Chung,et al.  Bronchoconstriction and airway microvascular leakage in guinea pigs sensitized with trimellitic anhydride. , 1992, The American review of respiratory disease.

[13]  J. Martin,et al.  Morphometric changes during the early airway response to allergen challenge in the rat. , 1992, The American review of respiratory disease.

[14]  K. Chung,et al.  Involvement of inflammatory mediators in the airway responses to trimellitic anhydride in sensitized guinea‐pigs , 1992, British journal of pharmacology.

[15]  R. Patterson,et al.  A clinical and immunologic study of employees in a facility manufacturing trimellitic anhydride. , 1992, Allergy proceedings : the official journal of regional and state allergy societies.

[16]  T. Fukuda,et al.  Airway hyperresponsiveness, increased intracellular spaces of bronchial epithelium, and increased infiltration of eosinophils and lymphocytes in bronchial mucosa in asthma. , 1992, The American review of respiratory disease.

[17]  J. Lötvall,et al.  Effect of dexamethasone and cyclosporin A on allergen-induced airway hyperresponsiveness and inflammatory cell responses in sensitized Brown-Norway rats. , 1992, The American review of respiratory disease.

[18]  E. Gelfand,et al.  Aerosolized antigen exposure without adjuvant causes increased IgE production and increased airway responsiveness in the mouse. , 1992, The Journal of allergy and clinical immunology.

[19]  R. Pauwels,et al.  Effect of acute and chronic antigen inhalation on airway morphology and responsiveness in actively sensitized rats. , 1992, The American review of respiratory disease.

[20]  K. Chung,et al.  Airway hyperresponsiveness is associated with inflammatory cell infiltration in allergic brown-Norway rats. , 1992, International archives of allergy and immunology.

[21]  J. Lötvall,et al.  Characterization of allergen-induced bronchial hyperresponsiveness and airway inflammation in actively sensitized brown-Norway rats. , 1991, The Journal of allergy and clinical immunology.

[22]  T. Stijnen,et al.  Effect of epithelial denudation, inflammatory mediators and mast cell activation on the sensitivity of isolated human airways to methacholine. , 1991, European journal of pharmacology.

[23]  S. Sapienza,et al.  Morphometry of the airways during late responses to antigen challenge in the rat. , 1991, The American review of respiratory disease.

[24]  L. Machado,et al.  Factors influencing the occurrence of late bronchial reactions after allergen challenge , 1990, Allergy.

[25]  J. Harris,et al.  A twelve-year clinical and immunologic evaluation of workers involved in the manufacture of trimellitic anhydride (TMA). , 1990, Allergy proceedings : the official journal of regional and state allergy societies.

[26]  A. Lindén,et al.  Epithelium-derived PGE2 inhibits the contractile response to cholinergic stimulation in isolated ferret trachea. , 1990, Pulmonary pharmacology.

[27]  H. G. Johnson,et al.  Ascaris suum ova-induced bronchoconstriction, eosinophilia, and IgE antibody responses in experimentally infected primates did not lead to histamine hyperreactivity. , 1989, The American review of respiratory disease.

[28]  J. Martin,et al.  Late airway responses to antigen challenge in sensitized inbred rats. , 1988, The American review of respiratory disease.

[29]  C. Plopper,et al.  Structure as revealed by airway dissection. A comparison of mammalian lungs. , 1983, The American review of respiratory disease.