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

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 290; no. 5; pp. L971 - L977
• Main Authors: Moriyama, Maiko, Fukuyama, Satoru, Inoue, Hiromasa, Matsumoto, Takafumi, Sato, Takahiro, Tanaka, Kentaro, Kinjyo, Ichiko, Kano, Tatsuhiko, Yoshimura, Akihiko, Kojima, Masayasu
• Format: Journal Article
• Language: English
• Published: United States 01.05.2006
• Subjects: Allergens; Animals; Bronchoalveolar Lavage Fluid - cytology; Calcium Signaling - physiology; Cell Adhesion - immunology; Cell Adhesion - physiology; Eosinophilia - immunology; Eosinophilia - pathology; Eosinophilia - physiopathology; Eosinophils - immunology; Eosinophils - pathology; Eosinophils - physiology; Macrophages, Alveolar - immunology; Macrophages, Alveolar - pathology; Macrophages, Alveolar - physiology; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - drug effects; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuropeptides - deficiency; Neuropeptides - genetics; Neuropeptides - physiology; Receptors, Neurotransmitter - antagonists & inhibitors; Receptors, Neurotransmitter - drug effects
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00345.2005

1 Department of Molecular Genetics, Institute of Life Sciences, Kurume University, Fukuoka; 2 Department of Anesthesiology, Kurume University School of Medicine, Fukuoka; and 3 Research Institute for Diseases of the Chest, Graduate School of Medical Sciences; and 4 Division 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 Ca 2+ 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 Address for reprint requests and other correspondence: M. Moriyama, Dept. of Molecular Genetics, Institute of Life Sciences, Kurume Univ., 1-1 Hyakunen-kohen, Kurume, Fukuoka 839-0864, Japan (e-mail: moriyama{at}lsi.kurume-u.ac.jp )