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    Targeting granulocyte‐macrophage colony‐stimulating factor in epithelial and vascular remodeling in experimental eosinophilic esophagitis


    McNamee, Eóin N. and Biette, K.A. and Hammer, J.A. and Harris, R. and Miyazawa, H. and Lee, James J. and Furuta, Glenn T. and Masterson, Joanne C. (2017) Targeting granulocyte‐macrophage colony‐stimulating factor in epithelial and vascular remodeling in experimental eosinophilic esophagitis. Allergy, 72. pp. 1232-1242. ISSN 1398-9995

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    Abstract

    Background: Eosinophilic esophagitis (EoE) is a chronic antigen‐mediated clinicopathologic disease of the esophagus characterized by an eosinophil‐predominant inflammatory infiltrate. A clinical hallmark is extensive tissue remodeling including basal zone hyperplasia, fibrosis, and angiogenesis. However, the cellular mechanisms responsible for these processes are not fully defined. We hypothesized that targeting granulocyte‐macrophage colony‐stimulating factor (GM‐CSF; an agonist cytokine linked with eosinophil survival and activation) would be protective in a preclinical model of EoE. Methods: Eosinophilic esophagitis‐like esophageal inflammation was induced in the L2‐IL5OXA EoE mouse model, and GM‐CSF production was assessed by mRNA and protein analyses. Granulocyte‐macrophage colony‐stimulating factor‐receptor‐alpha expression patterns were examined by flow cytometric and immunofluorescence analysis. L2‐IL5OXA EoE mice were treated with anti‐GM‐CSF neutralizing antibody or isotype control and assessed for histopathological indices of eosinophilia, epithelial hyperplasia, and angiogenesis by immunohistochemistry and RT‐PCR. Results: Significantly increased levels of esophageal GM‐CSF expression was detected in the L2‐IL5OXA mouse EoE model during active inflammation. Granulocyte‐macrophage colony‐stimulating factor‐receptor‐alpha was predominantly expressed on esophageal eosinophils during EoE, in addition to select cells within the lamina propria. Anti‐GM‐CSF neutralization in L2‐IL5OXA EoE mice resulted in a significant diminution of epithelial eosinophilia in addition to basal cell hyperplasia and vascular remodeling. This treatment response was independent of effects on esophageal eosinophil maturation or activation. Conclusion: Granulocyte‐macrophage colony‐stimulating factor is a potential therapeutic target to reduce esophageal eosinophilia and remodeling.

    Item Type: Article
    Additional Information: Cite as: McNamee EN, Biette KA, Hammer J, Harris R, Miyazawa H, Lee JJ, Furuta GT, Masterson JC. Targeting granulocyte-macrophage colonystimulating factor in epithelial and vascular remodeling in experimental eosinophilic esophagitis. Allergy 2017; 72: 1232–1242.
    Keywords: eosinophil; epithelial; esophagitis; granulocyte- macrophage colony-stimulating factor (GM-CSF); GM-CSF receptor;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Human Health Institute
    Item ID: 11666
    Identification Number: https://doi.org/10.1111/all.13105
    Depositing User: Joanne Masterson
    Date Deposited: 06 Nov 2019 17:29
    Journal or Publication Title: Allergy
    Publisher: Wiley
    Refereed: Yes
    URI:

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