Airway responses in Brown Norway rats following inhalation sensitization and challenge with trimellitic anhydride.
Trimellitic anhydride (TMA) is a cause of asthma in man. Dose-dependent TMA-specific IgE, histopathology, and airway responses after sensitization by inhalation were examined in the Brown Norway rat. Rats were exposed to 0.04, 0.4, 4, or 40 mg/m3 TMA aerosol for 10 min, once a week, over 10 weeks. All lower exposures were, subsequently, rechallenged to 40 mg/m3 TMA aerosol. All rats received a sham exposure 1 week prior to the first TMA exposure. Following the sham exposure and weekly after each TMA exposure, TMA-specific IgE and both early-phase airway response (EAR) and late-phase airway response (LAR) were measured using enhanced pause (Penh). All rats sensitized by 40 mg/m3 TMA developed specific IgE, EAR, and LAR to one or more of the challenges to 40 mg/m3 TMA. TMA of 4 mg/m3 induced a much lower, but stable, specific IgE response. EAR and LAR were observed only after a 40 mg/m3 TMA rechallenge in this group, but it was much larger than that observed in the 40 mg/m3 TMA-sensitized and challenged group. Exposure-dependent histopathological changes noted included eosinophilic granulomatous interstitial pneumonia, perivascular eosinophil infiltrates, bronchial-associated lymphoid tissue hyperplasia, and peribronchiolar plasma cell infiltrates.
Zhang
Xing-Dong
XD
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA.
Andrew
Michael E
ME
Hubbs
Ann F
AF
Siegel
Paul D
PD
D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects* / Q000502:physiology; D000485:Allergens / Q000276:immunology / Q000633:toxicity*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D001980:Bronchi / Q000187:drug effects* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D001985:Bronchial Provocation Tests; D005260:Female; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D019570:Inhalation Exposure; D010796:Phthalic Anhydrides / Q000276:immunology / Q000633:toxicity*; D010993:Plethysmography, Whole Body; D051381:Rats; D011914:Rats, Inbred BN; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D013047:Specific Pathogen-Free Organisms
D000485:Allergens; D000888:Antibodies, Anti-Idiotypic; D010796:Phthalic Anhydrides; D007073:Immunoglobulin E; C015559:trimellitic anhydride