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Eosinophil peroxidase activates cells by HER2 receptor engagement and ?1-integrin clustering with downstream MAPK cell signaling.


ABSTRACT: Eosinophils account for 1-3% of peripheral blood leukocytes and accumulate at sites of allergic inflammation, where they play a pathogenic role. Studies have shown that treatment with mepolizumab (an anti-IL-5 monoclonal antibody) is beneficial to patients with severe eosinophilic asthma, however, the mechanism of precisely how eosinophils mediate these pathogenic effects is uncertain. Eosinophils contain several cationic granule proteins, including Eosinophil Peroxidase (EPO). The main significance of this work is the discovery of EPO as a novel ligand for the HER2 receptor. Following HER2 activation, EPO induces activation of FAK and subsequent activation of ?1-integrin, via inside-out signaling. This complex results in downstream activation of ERK1/2 and a sustained up regulation of both MUC4 and the HER2 receptor. These data identify a receptor for one of the eosinophil granule proteins and demonstrate a potential explanation of the proliferative effects of eosinophils.

SUBMITTER: Hennigan K 

PROVIDER: S-EPMC5070911 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Eosinophil peroxidase activates cells by HER2 receptor engagement and β1-integrin clustering with downstream MAPK cell signaling.

Hennigan Kerrie K   Conroy Paul J PJ   Walsh Marie-Therese MT   Amin Mohamed M   Amin Mohamed M   O'Kennedy Richard R   Ramasamy Patmapriya P   Gleich Gerald J GJ   Siddiqui Zeshan Z   Glynn Senan S   McCabe Olive O   Mooney Catherine C   Harvey Brian J BJ   Costello Richard W RW   McBryan Jean J  

Clinical immunology (Orlando, Fla.) 20160809


Eosinophils account for 1-3% of peripheral blood leukocytes and accumulate at sites of allergic inflammation, where they play a pathogenic role. Studies have shown that treatment with mepolizumab (an anti-IL-5 monoclonal antibody) is beneficial to patients with severe eosinophilic asthma, however, the mechanism of precisely how eosinophils mediate these pathogenic effects is uncertain. Eosinophils contain several cationic granule proteins, including Eosinophil Peroxidase (EPO). The main signific  ...[more]

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