Development of eosinophilic airway inflammation and airway hyperresponsiveness requires interleukin-5 but not immunoglobulin E or B lymphocytes.
We previously defined a role for B cells and allergen-specific immunoglobulins in the development of allergic sensitization, airway inflammation, and airway hyperresponsiveness (AHR), using a 10-d protocol in which allergen exposure occurred exclusively via the airways, without adjuvant. In the present protocol, normal and B-cell-deficient (microMt(-/-)) mice were sensitized intraperitoneally to ovalbumin (OVA) and challenged with OVA via the airways in order to examine the requirements for AHR with this protocol. T-cell activation (antigen-specific proliferative responses and Th2-type cytokine production) and eosinophil infiltration in the peribronchial regions of the airways, with signs of eosinophil activation and degranulation, occurred in both experimental groups. In contrast to the 10-d protocol, increased in vivo airway responsiveness to methacholine and in vitro tracheal smooth-muscle responses to electrical field stimulation were observed in both normal and B-cell-deficient mice, and these responses were inhibited by anti-interleukin (IL)-5 administration before airway challenge. These data show that IL-5, but not B cells or allergen-specific IgE, are required for eosinophil airway infiltration and the development of AHR following allergen/alum sensitization and repeated airway challenge with allergen. These results emphasize that the use of different sensitization and challenge protocols can influence the requirements for development of AHR.
Hamelmann
E
E
Division of Basic Sciences and Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80260, USA.
Takeda
K
K
Schwarze
J
J
Vella
A T
AT
Irvin
C G
CG
Gelfand
E W
EW
D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000485:Allergens; D016207:Cytokines; D015848:Interleukin-5; D007073:Immunoglobulin E; D010047:Ovalbumin