An essential role of mast cells in the development of airway hyperresponsiveness in a murine asthma model.
Immunization of BALB/c mice with alum-adsorbed OVA, followed by three bronchoprovocations with aerosolized OVA, resulted in the development of airway hyperresponsiveness (AHR) and allergic inflammation in the lung accompanied by severe infiltration of eosinophils into airways. In this murine asthma model, administration of monoclonal anti-IL-5 Ab before each Ag challenge markedly inhibited airway eosinophilia, but the treatment did not affect the development of AHR. Immunization and aerosol challenges with OVA following the same protocol failed to induce AHR in the mast cell-deficient W/Wv mice, but induced AHR in their congenic littermates, i.e., WBB6F1 (+/+) mice. No significant difference was found between the W/Wv mice and +/+ mice with respect to the IgE and IgG1 anti-OVA Ab responses and to the airway eosinophilia after Ag provocations. It was also found that reconstitution of W/Wv mice with bone marrow-derived mast cells cultured from normal littermates restored the capacity of developing Ag-induced AHR, indicating that lack of mast cells was responsible for the failure of W/Wv mice to develop Ag-induced AHR under the experimental conditions. However, the OVA-immunized W/Wv mice developed AHR by increasing the frequency and Ag dose of bronchoprovocations. The results suggested that AHR could be developed by two distinct cellular mechanisms. One would go through mast cell activation and the other is IgE/mast cell independent but an eosinophil/IL-5-dependent mechanism.
Kobayashi
T
T
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan. k-tetsuto@kirin.co.jp
Miura
T
T
Haba
T
T
Sato
M
M
Serizawa
I
I
Nagai
H
H
Ishizaka
K
K
D000336:Aerosols; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000637:transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009330:Nebulizers and Vaporizers; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology
D000336:Aerosols; D010047:Ovalbumin