A murine model of allergic rhinitis: studies on the role of IgE in pathogenesis and analysis of the eosinophil influx elicited by allergen and eotaxin.
BACKGROUND
Allergic rhinitis is a prevalent disease with significant morbidity. Studies of its pathophysiology in human subjects have been limited. Nasal biopsy specimens are difficult to obtain, and nasal secretions incompletely reflect the cellular and molecular events in the mucosa. IgE-mediated mast cell activation and the elaboration of factors promoting eosinophil development and chemotaxis are likely to participate in pathogenesis.


OBJECTIVE
We sought to develop a murine model of allergic rhinitis, to use it to assess the role of IgE in pathogenesis, and to study the effects of IL-5 and eotaxin in the nasal mucosa.


METHODS
A protein extract of Aspergillus fumigatus (Af) was instilled intranasally in mice. Histologic changes were examined in wild-type and IgE-deficient (IgE-/-) animals. The effect of eotaxin administration was assessed in wild-type and IL-5 transgenic mice.


RESULTS
Af-treated mice developed a nasal mucosal eosinophil influx comparable to that described for humans. This histology was distinct from that observed in a murine model of Af-induced asthma. The pathology appeared over a time course similar to that reported for human subjects. There was no difference in the intensity of the mucosal inflammatory infiltrate of Af-treated IgE-/- mice compared with wild-type mice. Eotaxin was able to recruit eosinophils to the mucosa but only in IL-5 transgenic animals.


CONCLUSIONS
We describe a murine model for allergic rhinitis with an eosinophilic infiltrate comparable to that found in human disease and have demonstrated that rhinitis can arise in the absence of IgE. We have shown that the eosinophil influx can be induced by eotaxin in the presence of IL-5.
van de Rijn
M
M
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical System, Philadelphia, USA.
Mehlhop
P D
PD
Judkins
A
A
Rothenberg
M E
ME
Luster
A D
AD
Oettgen
H C
HC
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology*; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D009297:Nasal Mucosa / Q000276:immunology / Q000473:pathology; D012220:Rhinitis / Q000276:immunology*; D013997:Time Factors
D000485:Allergens; C515456:CCL11 protein, human; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D007073:Immunoglobulin E