title: Interleukin-33 enhances adhesion, CD11b expression and survival in human eosinophils.
abstract: Eosinophils are important effector cells in allergic diseases, but the mechanisms regulating their biological functions remain obscure. Interleukin-33 (IL-33) is a recently identified cytokine of the IL-1 family, and it reportedly accelerates the production of Th2-associated cytokines and promotes tissue inflammation. However, the action of IL-33 on effector cells such as eosinophils has remained unclear. In this study, we investigated the effects of IL-33 on eosinophil activation, assessed in terms of the cells' adhesiveness, expression of CD11b and apoptosis. Adhesiveness was quantified by measuring eosinophil peroxidase content of adherent eosinophils, and expression of CD11b was measured by flow cytometry. Apoptosis was determined by flow cytometry based on the ability of cells to bind annexin V. Real-time PCR analysis showed that eosinophils expressed mRNA for ST2, a putative receptor for IL-33. IL-33 at 1-100 ng/ml enhanced the adhesiveness and CD11b expression of eosinophils even more potently than IL-5. IL-33 maintained the viability of eosinophils. Treatment with neutralizing antibodies to ST2 eliminated the effects of IL-33 on eosinophil CD11b expression and cell survival. However, IL-33 did not elicit degranulation or leukotriene C4 synthesis in eosinophils. These findings indicate that IL-33 potently induces eosinophil adhesion and CD11b expression and enhances eosinophil survival. The IL-33-ST2 pathway might be an important regulator of eosinophil biology in the pathogenesis of Th2-biased allergic diseases.
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. fueta-tky@umin.ac.jp
authors.forename: Maho
authors.initials: M
authors.lastname: Suzukawa
authors.forename: Rikiya
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authors.lastname: Koketsu
authors.forename: Motoyasu
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authors.lastname: Iikura
authors.forename: Susumu
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authors.lastname: Nakae
authors.forename: Kenji
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authors.lastname: Matsumoto
authors.forename: Hiroyuki
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authors.forename: Hirohisa
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authors.lastname: Saito
authors.forename: Kouji
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authors.lastname: Matsushima
authors.forename: Ken
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authors.lastname: Ohta
authors.forename: Kazuhiko
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authors.lastname: Yamamoto
authors.forename: Masao
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authors.lastname: Yamaguchi