Integrin α5 interacts with EGFR, is necessary for Fce{open}RI signaling and is necessary for allergic inflammation in relation with angiogenesis

Youngmi Kim; Kyungjong Kim; Deokbum Park; Sangkyung Eom; Hyunmi Park; Hansoo Lee; Yun Sil Lee; Jongseon Choe; Jang Hee Hahn; Young Myeong Kim; Jai Youl Ro; Dooil Jeoung

doi:10.1016/j.molimm.2011.01.013

Integrin α₅ interacts with EGFR, is necessary for Fce{open}RI signaling and is necessary for allergic inflammation in relation with angiogenesis

Youngmi Kim, Kyungjong Kim, Deokbum Park, Sangkyung Eom, Hyunmi Park, Hansoo Lee, Yun Sil Lee, Jongseon Choe, Jang Hee Hahn, Young Myeong Kim, Jai Youl Ro, Dooil Jeoung

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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 α₅ 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 Fce{open}RI 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 α₅ were found to be necessary for IgE-dependent cutaneous anaphylaxis. FAK (focal adhesion kinase), interacted with EGFR and with Fce{open}RI upon antigen stimulation, and it was necessary for the increased secretion of β-hexosaminidase in both RBL2H3 cells and BMMCs. EGFR and integrin α₅ 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 α₅. In conclusion, EGFR, via interaction with Fce{open}RI and integrin α₅, is necessary for allergic inflammation associated with cellular interaction.

Original language	English
Pages (from-to)	1035-1045
Number of pages	11
Journal	Molecular Immunology
Volume	48
Issue number	8
DOIs	https://doi.org/10.1016/j.molimm.2011.01.013
State	Published - Apr 2011

Bibliographical note

Funding Information:
This work was supported by a grant from the Korea Research Foundation ( C1001478-01-01 , C1006272-01-01 , C1006625-01-02 and C1007565-01-01 ). This work was supported by the Regional Innovation Center Program of the Ministry of Education, Science and Technology. This work was also supported by a grant from Korea Research Foundation Grant funded by the Korean Government (MEST) (The Regional Research Universities Program/Medical & Bio-Materials Research Center).

Keywords

Allergic inflammation
Angiogenesis
EGFR
Fce{open}RI
Integrin

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10.1016/j.molimm.2011.01.013

Cite this

@article{b19dd7659ae14ee5bc9ef497f8809c7a,

title = "Integrin α5 interacts with EGFR, is necessary for Fce{open}RI 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 α5 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 Fce{open}RI 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 α5 were found to be necessary for IgE-dependent cutaneous anaphylaxis. FAK (focal adhesion kinase), interacted with EGFR and with Fce{open}RI upon antigen stimulation, and it was necessary for the increased secretion of β-hexosaminidase in both RBL2H3 cells and BMMCs. EGFR and integrin α5 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 α5. In conclusion, EGFR, via interaction with Fce{open}RI and integrin α5, is necessary for allergic inflammation associated with cellular interaction.",

keywords = "Allergic inflammation, Angiogenesis, EGFR, Fce{open}RI, Integrin",

author = "Youngmi Kim and Kyungjong Kim and Deokbum Park and Sangkyung Eom and Hyunmi Park and Hansoo Lee and Lee, {Yun Sil} and Jongseon Choe and Hahn, {Jang Hee} and Kim, {Young Myeong} and Ro, {Jai Youl} and Dooil Jeoung",

note = "Funding Information: This work was supported by a grant from the Korea Research Foundation ( C1001478-01-01 , C1006272-01-01 , C1006625-01-02 and C1007565-01-01 ). This work was supported by the Regional Innovation Center Program of the Ministry of Education, Science and Technology. This work was also supported by a grant from Korea Research Foundation Grant funded by the Korean Government (MEST) (The Regional Research Universities Program/Medical & Bio-Materials Research Center). ",

year = "2011",

month = apr,

doi = "10.1016/j.molimm.2011.01.013",

language = "English",

volume = "48",

pages = "1035--1045",

journal = "Molecular Immunology",

issn = "0161-5890",

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TY - JOUR

T1 - Integrin α5 interacts with EGFR, is necessary for Fce{open}RI signaling and is necessary for allergic inflammation in relation with angiogenesis

AU - Kim, Youngmi

AU - Kim, Kyungjong

AU - Park, Deokbum

AU - Eom, Sangkyung

AU - Park, Hyunmi

AU - Lee, Hansoo

AU - Lee, Yun Sil

AU - Choe, Jongseon

AU - Hahn, Jang Hee

AU - Kim, Young Myeong

AU - Ro, Jai Youl

AU - Jeoung, Dooil

N1 - Funding Information: This work was supported by a grant from the Korea Research Foundation ( C1001478-01-01 , C1006272-01-01 , C1006625-01-02 and C1007565-01-01 ). This work was supported by the Regional Innovation Center Program of the Ministry of Education, Science and Technology. This work was also supported by a grant from Korea Research Foundation Grant funded by the Korean Government (MEST) (The Regional Research Universities Program/Medical & Bio-Materials Research Center).

PY - 2011/4

Y1 - 2011/4

N2 - 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 α5 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 Fce{open}RI 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 α5 were found to be necessary for IgE-dependent cutaneous anaphylaxis. FAK (focal adhesion kinase), interacted with EGFR and with Fce{open}RI upon antigen stimulation, and it was necessary for the increased secretion of β-hexosaminidase in both RBL2H3 cells and BMMCs. EGFR and integrin α5 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 α5. In conclusion, EGFR, via interaction with Fce{open}RI and integrin α5, is necessary for allergic inflammation associated with cellular interaction.

AB - 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 α5 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 Fce{open}RI 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 α5 were found to be necessary for IgE-dependent cutaneous anaphylaxis. FAK (focal adhesion kinase), interacted with EGFR and with Fce{open}RI upon antigen stimulation, and it was necessary for the increased secretion of β-hexosaminidase in both RBL2H3 cells and BMMCs. EGFR and integrin α5 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 α5. In conclusion, EGFR, via interaction with Fce{open}RI and integrin α5, is necessary for allergic inflammation associated with cellular interaction.

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KW - Angiogenesis

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