A study on the mechanism of mucosal mast cells invasion into intestinal epithelium during nematode infection

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Mucosal-type mast cells (MMC) in the respiratory and/or gut epithelium play pivotal roles in the development of allergic inflammation and nematode clearance. We previously reported that murine bone marrow-derived mast cells (BMMC) express E-cadherin that could be involved in homophilic binding with epithelial cell E-cadherin. We examined whether E-cadherin is also expressed in human mast cell HMC-1. E-cadherin expression in HMC-1 was confirmed by immunoblotting as well as by FACS analyses. In the presence of E-cadherin blocking antibody or a synthetic E-cadherin decapeptide in culture medium, adhesion of HMC-1 cells to A431 epithelial cells was slightly but significantly suppressed. Next, to determine the role of E-cadherin and αEβ7 integrin in MMC localization to the epithelium, we analyzed the epithelial binding of BMMC developed with SCF, IL-3,IL-9 and TGF-β1. These BMMC were similar to mature MMC in terms of mouse mast cell protease (mMCP)-1 expression. FACS analyses revealed that MMC-like BMMC expressed αEβ7 integrin as well as E-cadherin. The adhesion was suppressed significantly by the combined addition of blocking antibodies against integrin αE and E-cadherin to F9 epithelial cells. Immunofluorescence studies of the jejunum obtained from nematode-infected mice demonstrated that c-kit^+ intraepithelial MMC expressed integrin αEβ7. These results suggested that E-cadherin and αEβ7 integrin, which are expressed on MMC-analog BMMC or MMC play an important role in mast cell-epithelial cell interaction through homophilic as well as heterophilic binding to the epithelial E-cadherin molecule.