Integrin α5 interacts with EGFR, is necessary for FcεRI signaling and is necessary for allergic inflammation in relation with angiogenesis

초록

Recent reports have suggested role for epidermal growth factor receptor (EGFR) in asthma and skin inflammation. Integrin(s) are known to be necessary for the transactivation of EGER. The roles of EGFR and integrin(s) in allergic inflammation were investigated. Antigen stimulation induced activation of EGFR and interaction between EGFR and integrin alpha(5) in Rat Basophilic Leukemia (RBL2H3) cells and bone marrow-derived mouse mast cells (BMMCs). Flow cytometry revealed increased phosphorylation of EGFR on cell surfaces. Antigen stimulation induced interaction between EGFR and Fc epsilon RI in both RBL2H3 cells and BMMCs. Blocking of EGFR or integrin alpha exerted negative effects on rac1 activity and secretion of beta-hexosaminidase in both RBL2H3 cells and BMMCs. EGFR and integrin alpha(5) were found to be necessary for IgE-dependent cutaneous anaphylaxis. FAK (focal adhesion kinase), interacted with EGFR and with Fc epsilon RI upon antigen stimulation, and it was necessary for the increased secretion of beta-hexosaminidase in both RBL2H3 cells and BMMCs. EGFR and integrin alpha(5) were necessary for interactions between activated RBL2H3 cells, BMMCs and rat aortic endothelial cells (RAECs). Conditioned medium of antigen-stimulated RBL2H3 cells promoted RAECs tube formation, rat aortic ring formation and blood vessel formation. Conditioned medium of antigen-stimulated BMMCs also had the same effects on RAECs. This enhanced angiogenic potential of RAECs was dependent on EGFR and integrin alpha(5). In conclusion, EGFR, via interaction with Fc epsilon RI and integrin alpha(5), is necessary for allergic inflammation associated with cellular interaction. (C) 2011 Elsevier Ltd. All rights reserved.

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