Basophils store a variety of bioactive molecules including proteases in the secretory granules, and rapidly release them upon degranulation which contributes to allergic responses or host defense against pathogens. Mouse mast cell protease-8 (mMCP-8) is specifically expressed in murine basophils and widely accepted as a basophil-specific marker in mice. However, the physiological function of mMCP-8 has not been elucidated. In the present study, we show evidence that mMCP-8 provokes an inflammatory response in the skin lesion. mMCP-8 was localized to the secretory granules in basophils and released promptly after IgE/antigen-induced degranulation. Notably, subcutaneous injection of recombinant mMCP-8 (rmMCP-8) caused transient skin swelling associated with increased microvascular permeability and the local accumulation of leukocytes such as neutrophils, macrophages, and eosinophils.
Consistent with this, the increased expressions of chemokines such as CXCL1, CCL2, and CCL24 were detectable in the rmMCP-8-injected skin lesions. Interestingly, cyclooxygenase inhibitor abolished the mMCP-8-induced ear swelling and an increase in vascular permeability even though leukocyte accumulation was not affected by the same treatment. Collectively, our results suggest that mMCP-8 secreted by basophils plays an important role in IgE/antigen-induced skin inflammation by triggering the cyclooxygenase-dependent production of chemokines.