Peer-Reviewed Journal Details
Mandatory Fields
McNamee, EN;Biette, KA;Hammer, J;Harris, R;Miyazawa, H;Lee, JJ;Furuta, GT;Masterson, JC
2017
August
Allergy: European Journal of Allergy and Clinical Immunology
Targeting granulocyte-macrophage colony-stimulating factor in epithelial and vascular remodeling in experimental eosinophilic esophagitis
Published
2 ()
Optional Fields
GM-CSF RHEUMATOID-ARTHRITIS ENDOTHELIAL-CELLS MOUSE MODEL IL-5 MICE INFLAMMATION KERATINOCYTES PREVALENCE MECHANISM
72
1232
1242
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-IL5(OXA) 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-IL5(OXA) 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-IL5(OXA) 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-IL5(OXA) 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.
HOBOKEN
0105-4538
10.1111/all.13105
Grant Details