title: Integrin α(5) interacts with EGFR, is necessary for FcɛRI signaling and is necessary for allergic inflammation in relation with angiogenesis.
abstract: 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 EGFR. The roles of EGFR and integrin(s) in allergic inflammation were investigated. Antigen stimulation induced activation of EGFR and interaction between EGFR and integrin α(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 FcɛRI in both RBL2H3 cells and BMMCs. Blocking of EGFR or integrin α exerted negative effects on rac1 activity and secretion of β-hexosaminidase in both RBL2H3 cells and BMMCs. EGFR and integrin α(5) were found to be necessary for IgE-dependent cutaneous anaphylaxis. FAK (focal adhesion kinase), interacted with EGFR and with FcɛRI upon antigen stimulation, and it was necessary for the increased secretion of β-hexosaminidase in both RBL2H3 cells and BMMCs. EGFR and integrin α(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 α(5). In conclusion, EGFR, via interaction with FcɛRI and integrin α(5), is necessary for allergic inflammation associated with cellular interaction.
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Kim
authors.forename: Kyungjong
authors.initials: K
authors.lastname: Kim
authors.forename: Deokbum
authors.initials: D
authors.lastname: Park
authors.forename: Sangkyung
authors.initials: S
authors.lastname: Eom
authors.forename: Hyunmi
authors.initials: H
authors.lastname: Park
authors.forename: Hansoo
authors.initials: H
authors.lastname: Lee
authors.forename: Yun-Sil
authors.initials: YS
authors.lastname: Lee
authors.forename: Jongseon
authors.initials: J
authors.lastname: Choe
authors.forename: Jang-Hee
authors.initials: JH
authors.lastname: Hahn
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Jai Youl
authors.initials: JY
authors.lastname: Ro
authors.forename: Dooil
authors.initials: D
authors.lastname: Jeoung
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D039482:Integrin alpha5 / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: C553474:FCER1A protein, rat; D039482:Integrin alpha5; D017455:Receptors, IgE; D066246:ErbB Receptors; D051416:Focal Adhesion Protein-Tyrosine Kinases; D001619:beta-N-Acetylhexosaminidases; D020830:rac1 GTP-Binding Protein