Changes in asthma-like responses after extended removal from exposure to trimellitic anhydride in the Brown Norway rat model
Article first published online: 22 JUN 2009
Published 2009. This article is a US Government work and is in the public domain in the USA
Clinical & Experimental Allergy
Volume 39, Issue 11, pages 1746–1753, November 2009
How to Cite
Zhang, X. D., Hubbs, A. F. and Siegel, P. D. (2009), Changes in asthma-like responses after extended removal from exposure to trimellitic anhydride in the Brown Norway rat model. Clinical & Experimental Allergy, 39: 1746–1753. doi: 10.1111/j.1365-2222.2009.03304.x
- Issue published online: 21 OCT 2009
- Article first published online: 22 JUN 2009
- Submitted 15 September 2008; revised 20 April 2009; accepted 8 May 2009
- Brown Norway rat;
- persistent occupational asthma;
- skin/dermal exposure;
- trimellitic anhydride
Background Organic acid anhydride-induced occupational asthma is considered to be IgE-mediated. Airway and skin exposure are the two main routes of sensitization in the work place. Recently we developed an allergic asthmatic Brown Norway rat model sensitized by dermal exposure to trimellitic anhydride (TMA) using an occlusion patch application.
Objectives The objectives of this study were (1) to develop a model of non-occluded dermal exposure leading to allergic sensitization and (2) to examine the effect of extended removal from exposure on persistence of both specific IgE and TMA aerosol-induced airway responses in this model.
Methods TMA powder (4 or 40 mg) was applied, unoccluded, to the skin of rats for 4 h, once/week for 4 weeks. Rats were given a 10-min aerosol challenge to 40 mg/m3 TMA 2 weeks after the last dermal exposure (day 35). Another group was challenged on day 35 and again 18–24 months later. Respiratory enhanced pause (Penh), pulmonary histopathology and inflammation and specific IgE titres were measured.
Results Rats produced dose-dependent specific IgE titres after exposure and developed early-phase (EAR) and late-phase airway responses (LAR) after airway challenge to TMA aerosol as well as airway eosinophilic inflammation. Specific airway responses were still manifested after a second TMA airway challenge given 18–24 months following the initial airway challenge. While persistent, airway inflammation, specific IgE and EAR were significantly attenuated following the second TMA challenge. LAR remained robust at 18–24 months and was not significantly different from the response on day 35.
Conclusions These results demonstrate the persistence of chemical sensitization and further suggest that IgE is not essential for LAR.