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Mast Cells Can Amplify Airway Reactivity and Features of Chronic Inflammation in an Asthma Model in Mice

Correspondence to: Stephen J. Galli, Department of Pathology, L-235, Stanford University Medical Center, 300 Pasteur Dr., Palo Alto, CA 94305-5324. Tel:650-723-7975 Fax:650-725-6902 E-mail:sgalli{at}leland.stanford.edu.

The importance of mast cells in the development of the allergen-induced airway hyperreactivity and inflammation associated with asthma remains controversial. We found that genetically mast cell–deficient WBB6F₁-W/W^v mice that were sensitized to ovalbumin (OVA) without adjuvant, then challenged repetitively with antigen intranasally, exhibited much weaker responses in terms of bronchial hyperreactivity to aerosolized methacholine, lung tissue eosinophil infiltration, and numbers of proliferating cells within the airway epithelium than did identically treated WBB6F₁-+/+ normal mice. However, W/W^v mice that had undergone selective reconstitution of tissue mast cells with in vitro–derived mast cells of congenic +/+ mouse origin exhibited airway responses that were very similar to those of the +/+ mice. By contrast, W/W^v mice that were sensitized with OVA emulsified in alum and challenged with aerosolized OVA exhibited levels of airway hyperreactivity and lung tissue eosinophil infiltration that were similar to those of the corresponding +/+ mice. Nevertheless, these W/W^v mice exhibited significantly fewer proliferating cells within the airway epithelium than did identically treated +/+ mice. These results show that, depending on the "asthma model" investigated, mast cells can either have a critical role in, or not be essential for, multiple features of allergic airway responses in mice.

Key Words: eosinophil, epithelium, hyperresponsiveness, tissue remodeling, T lymphocyte

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