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 bronc hoprovocations 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 m arkedly 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/W-v mi ce, but induced AHR in their congenic littermates, i.e., WBB6F(1) (+/+) mic e. No significant difference was found between the W/W-v mice and +/+ mice with respect to the IgE and IgG1 anti-OVA Ab responses and to the airway eo sinophilia after Ag provocations. It was also found that reconstitution of W/W-v mice with bone marrow-derived mast cells cultured from normal litterm ates restored the capacity of developing Ag-induced AHR, indicating that la ck of mast cells was responsible for the failure of W/W-v mice to develop A g-induced AHR under the experimental conditions. However, the OVA-immunized W/W-v mice developed AHR by increasing the frequency and Ag dose of bronch oprovocations. The results suggested that AHR could be developed by two dis tinct cellular mechanisms. One would go through mast cell activation and th e other is IgE/mast cell independent but an eosinophil/IL-5 dependent mecha nism.