Mast cells can promote the development of multiple features of chronic asthma in mice

Bronchial asthma, the most prevalent cause of significant respiratory morbidity in the developed world, typically is a chronic disorder associated with long-term changes in the airways. We developed a mouse model of chronic asthma that results in markedly increased numbers of airway mast cells, enhanced airway responses to methacholine or antigen, chronic inflammation including infiltration with eosinophils and lymphocytes, airway epithelial goblet cell hyperplasia, enhanced expression of the mucin genes Muc5ac and Muc5b, and increased levels of lung collagen. Using mast cell-deficient (Kit(W-sb/W-sb) and/or Kit(W/W-v)) mice engrafted with FcR gamma(+/+) or FcR gamma(-/-) mast cells, we found that mast cells were required for the full development of each of these features of the model. However, some features also were expressed, although usually at less than wild-type levels, in mice whose mast cells lacked FcR gamma and therefore could not be activated by either antigen- and IgE-dependent aggregation of Fc epsilon RI or the binding of antigen-IgG1 immune complexes to Fc gamma RIII. These findings demonstrate that mast cells can contribute to the development of multiple features of chronic asthma in mice and identify both FcR gamma-dependent and FcR gamma-independent pathways of mast cell activation as important for the expression of key features of this asthma model.