Spatial and temporal expression of CCR3 and the common beta chain of the IL-3, IL-5 and GM-CSF receptor in the nasal epithelium and lymphoid tissues in a rat model of allergic rhinitis

Background: Allergic rhinitis (AR) and asthma are closely related conditions that often co-exist, and are characterized by a Th2 inflammatory response where eosinophils occupy a predominant role. Strategies aimed at blocking signaling through the CC chemokine receptor 3 (CCR3) and/or the common beta chain of the IL-3, IL-5 and GM-CSF receptor (pc) efficiently reduced eosinophilic inflammation in both animal models and in asthmatic patients. This study was therefore aimed at characterizing the spatio-temporal expression pattern of beta c and CCR3 using a rat model of AR. Methods: Sensitized rats were challenged with ovalbumin and sacrificed at 2 h, 8 h, 16 h or 24 h post-challenge. Nasal tissues were microdissected and used for mRNA quantification by QPCR, while histological evaluation determined the presence of eosinophils and mucosubstances. Results: Allergen-induced recruitment of eosinophils in the distal septum and turbinates was maximal at 8 h post-challenge, and was correlated with 2-4-fold increase in CCR3 and beta C mRNA. Recruitment of eosinophils was also accompanied by upregulated IL-5, IL-4R alpha, INF-alpha and IFN-gamma mRNA at early time-points. In contrast, IL-13 and MUC5AC mRNA, as well as production of mucosubstances were maximal at 24 h. Conclusions: beta c and CCR3 could play important roles in the modulation of the allergic response, and their inhibition may represent a promising therapeutic approach for AR. (C) 2010 Elsevier Ltd. All rights reserved.