Allergen-induced bronchial hyperreactivity and eosinophilic inflammation occur in the absence of IgE in a mouse model of asthma.
In patients with asthma, elevations of IgE correlate both with allergic inflammation of the airways and with bronchial hyperreactivity (BHR). Several investigations, using mouse models of this disease, have indicated a central role for IgE in the pathogenesis of the eosinophilic inflammation as well as in the obstructive airway physiology of BHR. Some diagnostic studies and therapeutic strategies for asthma are based on the putative role of IgE in asthma pathogenesis. Here, we use mice with a null mutation of the C epsilon locus to show that bronchial inflammation and BHR in response to allergen inhalation both can occur in the absence of IgE. We demonstrate that the eosinophilic bronchial inflammation elicited in an established mouse model of hypersensitivity to Aspergillus fumigatus (Af) is accompanied by the asthmatic physiology of BHR. Wild-type and IgE-deficient mice were sensitized intranasally with Af extract. Both groups of animals developed bronchoalveolar lavage eosinophilia and pulmonary parenchymal eosinophilia. This was accompanied by increased serum levels of total and Af-specific IgE in the wild-type animals only. This Af-sensitization protocol resulted in significant BHR in both wild-type mice and IgE-deficient mice. Interestingly, unsensitized IgE-deficient mice had increased bronchial responsiveness compared with unsensitized wild-type controls. We conclude that BHR and airways inflammation can be fully expressed via IgE-independent mechanisms. These may involve the activation of mast cells by factors other than IgE as well as a mucosal lymphocyte-mediated immune response to allergen.
Mehlhop
P D
PD
Division of Immunology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
van de Rijn
M
M
Goldberg
A B
AB
Brewer
J P
JP
Kurup
V P
VP
Martin
T R
TR
Oettgen
H C
HC
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology*; D005803:Genes, Immunoglobulin; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood* / Q000235:genetics; D007249:Inflammation; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D012129:Respiratory Function Tests
D000485:Allergens; D000946:Antigens, Fungal; D007073:Immunoglobulin E