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PLoS One. 2012;7(6):e39673. doi: 10.1371/journal.pone.0039673. Epub 2012 Jun 28.

IL-4 engagement of the type I IL-4 receptor complex enhances mouse eosinophil migration to eotaxin-1 in vitro.

Author information

1
Department of Microbiology and Immunology and the Center for Vascular and Inflammatory Diseases, The University of Maryland School of Medicine, Baltimore, Maryland, United States of America.

Abstract

BACKGROUND:

Previous work from our laboratory demonstrated that IL-4Rα expression on a myeloid cell type was responsible for enhancement of Th2-driven eosinophilic inflammation in a mouse model of allergic lung inflammation. Subsequently, we have shown that IL-4 signaling through type I IL-4 receptors on monocytes/macrophages strongly induced activation of the IRS-2 pathway and a subset of genes characteristic of alternatively activated macrophages. The direct effect(s) of IL-4 and IL-13 on mouse eosinophils are not clear. The goal of this study was determine the effect of IL-4 and IL-13 on mouse eosinophil function.

METHODS:

Standard Transwell chemotaxis assay was used to assay migration of mouse eosinophils and signal transduction was assessed by Western blotting.

RESULTS:

Here we determined that (i) mouse eosinophils express both type I and type II IL-4 receptors, (ii) in contrast to human eosinophils, mouse eosinophils do not chemotax to IL-4 or IL-13 although (iii) pre-treatment with IL-4 but not IL-13 enhanced migration to eotaxin-1. This IL-4-mediated enhancement was dependent on type I IL-4 receptor expression: γC-deficient eosinophils did not show enhancement of migratory capacity when pre-treated with IL-4. In addition, mouse eosinophils responded to IL-4 with the robust tyrosine phosphorylation of STAT6 and IRS-2, while IL-13-induced responses were considerably weaker.

CONCLUSIONS:

The presence of IL-4 in combination with eotaxin-1 in the allergic inflammatory milieu could potentiate infiltration of eosinophils into the lungs. Therapies that block IL-4 and chemokine receptors on eosinophils might be more effective clinically in reducing eosinophilic lung inflammation.

PMID:
22761864
PMCID:
PMC3386270
DOI:
10.1371/journal.pone.0039673
[Indexed for MEDLINE]
Free PMC Article

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