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This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: 290/5/L971    most recent 00345.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Moriyama, M. Articles by Kojima, M. Search for Related Content PubMed PubMed Citation Articles by Moriyama, M. Articles by Kojima, M.

The neuropeptide neuromedin U activates eosinophils and is involved in allergen-induced eosinophilia

¹Department of Molecular Genetics, Institute of Life Sciences, Kurume University, Fukuoka; ²Department of Anesthesiology, Kurume University School of Medicine, Fukuoka; and ³Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; and ⁴Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

Submitted 10 August 2005 ; accepted in final form 20 December 2005

Neuromedin U (NMU) is a neuropeptide expressed not only in the central nervous system but also in various organs, including the gastrointestinal tract and lungs. NMU interacts with two G protein-coupled receptors, NMU-R1 and NMU-R2. Although NMU-R2 is expressed in a specific region of the brain, NMU-R1 is expressed in various peripheral tissues, including immune and hematopoietic cells. Our recent study demonstrated an important role of NMU in mast cell-mediated inflammation. In this study, we showed that airway eosinophilia was reduced in NMU-deficient mice in an allergen-induced asthma model. There were no differences in the antigen-induced Th2 responses between wild-type and NMU knockout mice. NMU-R1 was highly expressed in the eosinophil cell line, and NMU directly induced Ca²⁺ mobilization and extracellular/signal-regulated kinase phosphorylation. NMU also induced cell adhesion to components of the extracellular matrix (fibronectin and collagen type I), and chemotaxis in vitro. Furthermore, NMU-R1 was also expressed in human peripheral blood eosinophils, and NMU induced cell adhesion in a dose-dependent manner. These data indicate that NMU promotes eosinophil infiltration into inflammatory sites by directly activating eosinophils. Our study suggests that NMU receptor antagonists could be novel targets for pharmacological inhibition of allergic inflammatory diseases, including asthma.

asthma models; knockout mouse; airway inflammation; cell adhesion; chemotaxis