Prolonged allergen challenge in murine nasal allergic rhinitis: nasal airway remodeling and adaptation of nasal airway responsiveness.
BACKGROUND
Nasal airway remodeling exists in allergic rhinitis, but it appears to be far less extensive than in asthma. However, there has been little study about nasal airway remodeling and no study using mice models. It has been reported that airway hyperresponsiveness decreased after prolonged allergen challenge in a chronic murine asthma model together with the progression of remodeling. However, there has been no study of the relation of remodeling and airway responsiveness in nasal allergy. Therefore, we have undertaken this investigation to characterize nasal airway structural changes after prolonged allergen challenge and to examine the relationship between nasal airway hyperresponsivity and remodeling.


METHODS
We prepared murine allergic rhinitis for ovalbumin. Mice were subsequently challenged three times a week with ovalbumin from day 19 to days 53, 88, and 130. We examined allergen-induced nasal symptoms and objective nasal hyperresponsiveness using the enhanced pause system. Moreover, the pathologic changes were investigated after allergen challenge.


RESULTS
The extended allergen challenge protocol caused significant nasal airway remodeling. Specifically, remodeling was characterized by goblet cell hyperplasia and deposition of collagen in the submucosal area. Allergen-induced nasal hyperresponsiveness was first increased but gradually decreased in nasal symptoms and Penh after prolonged allergen challenge.


CONCLUSIONS
We have demonstrated that a remodeling of nasal mucosa in a murine allergic rhinitis model prolonged allergen exposure. Moreover, prolonged allergen exposure induced a reduction of nasal hyperresponsiveness together with a progression of nasal remodeling.
Nakaya
Muneo
M
Department of Otolaryngology, Faculty of Medicine, University of Tokyo, Tokyo, Japan. muneo@interlink.or.jp
Dohi
Makoto
M
Okunishi
Katsuhide
K
Nakagome
Kazuyuki
K
Tanaka
Ryoichi
R
Imamura
Mitsuru
M
Yamamoto
Kazuhiko
K
Kaga
Kimitaka
K
D000222:Adaptation, Physiological; D000485:Allergens / Q000276:immunology*; D000704:Analysis of Variance; D000818:Animals; D003094:Collagen / Q000276:immunology; D020397:Goblet Cells / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology / Q000473:pathology*; D010047:Ovalbumin / Q000276:immunology; D012220:Rhinitis / Q000276:immunology / Q000473:pathology*
D000485:Allergens; D010047:Ovalbumin; D003094:Collagen