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 (βc) 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 βc and CCR3 using a rat model of AR.


METHODS
Sensitized rats were challenged with ovalbumin and sacrificed at 2h, 8h, 16h or 24h 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 8h post-challenge, and was correlated with 2-4-fold increase in CCR3 and βc mRNA. Recruitment of eosinophils was also accompanied by upregulated IL-5, IL-4Rα, TNF-α and IFN-γ mRNA at early time-points. In contrast, IL-13 and MUC5AC mRNA, as well as production of mucosubstances were maximal at 24h.


CONCLUSIONS
βc and CCR3 could play important roles in the modulation of the allergic response, and their inhibition may represent a promising therapeutic approach for AR.
Fortin
Marylène
M
Topigen Pharmaceuticals Inc./Pharmaxis Ltd Group, 2901 East Rachel Street, Montreal, Quebec, Canada.
Wagner
James G
JG
Brault
Julie
J
Harkema
Jack R
JR
Renzi
Paolo M
PM
Paquet
Luc
L
Ferrari
Nicolay
N
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000378:metabolism*; D007377:Interleukin-3 / Q000235:genetics / Q000378:metabolism*; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000378:metabolism*; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D054397:Receptors, CCR3 / Q000235:genetics / Q000378:metabolism*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D012220:Rhinitis / Q000378:metabolism*
C515352:Ccr3 protein, rat; D017931:DNA Primers; D007377:Interleukin-3; D015848:Interleukin-5; D012333:RNA, Messenger; D054397:Receptors, CCR3; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor