Clinical & Experimental Allergy

The α4bβ7-integrin is dynamically expressed on murine eosinophils and involved in eosinophil trafficking to the intestine

Authors

  • E. B. Brandt,

    1. Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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  • N. Zimmermann,

    1. Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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  • E. E. Muntel,

    1. Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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  • Y. Yamada,

    1. Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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  • S. M. Pope,

    1. Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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  • A. Mishra,

    1. Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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  • S. P. Hogan,

    1. Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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  • M. E. Rothenberg

    1. Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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Correspondence:
Marc Rothenberg, M.D., Ph.D., Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
E-mail: Rothenberg@cchmc.org

Summary

Background Of the numerous adhesion molecules expressed by eosinophils, the α4-integrin has been identified as critically involved in eosinophil trafficking in the lung. Most studies have focused on the role of the α4β1-adhesion complex, but eosinophils also express the α4β7-integrin complex.

Objective To investigate the role of α4β7, by assessing its membrane expression on eosinophils from different compartments using allergen-challenged mice and IL-4/IL-5 bi-transgenic mice. In addition, we aim to determine the impact of β7-integrin deficiency on eosinophil recruitment to the lungs and intestine in specific experimental allergic models.

Results Evaluation of α4β7 expression on bronchoalveolar lavage fluid (BALF) and lung tissue eosinophils revealed a down-regulation of this integrin as eosinophils migrate through the lungs. Indeed eosinophils isolated from the BALF and lung of allergic mice had low expression of the α4β7-complex. While expression of the α4-chain remained unchanged, a significant decrease in β7-surface expression was observed. Intestinal eosinophils, isolated from Peyer's patches, also displayed a down-regulation of the α4β7-integrin, albeit only modest. In contrast, circulating eosinophils, isolated from the blood and spleen, expressed high levels of the α4β7-integrin. However, eosinophil trafficking into the lungs of β7-integrin-deficient mice was not significantly impaired in response to respiratory allergen challenges. In contrast, β7-deficient mice had impaired eosinophil recruitment to the intestine.

Conclusion Taken together, these results identify differential expression of the α4β7-integrin on eosinophils and its critical role in regulating eosinophil responses in the intestine.

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