The neuropeptide neuromedin U activates eosinophils and is involved in allergen-induced eosinophilia
The neuropeptide neuromedin U activates eosinophils and is involved in allergen-induced eosinophilia
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DOI：
10.1152/ajplung.00345.2005
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发表时间：
2006-05-01
影响因子：
4.9
通讯作者：
Kojima, M
中科院分区：
文献类型：
--
作者：
Moriyama, M;Fukuyama, S;Kojima, M
神经介肽U（NMU）是一种不仅在中枢神经系统中表达，而且在各种器官（包括胃肠道和肺）中表达的神经肽。NMU与两种G蛋白偶联受体NMU-R1和NMU-R2相互作用。虽然NMU-R2在大脑的特定区域中表达，但NMU-R1在各种外周组织中表达，包括免疫和造血细胞。我们最近的研究表明NMU在肥大细胞介导的炎症中发挥重要作用。在这项研究中，我们发现在过敏原诱导的哮喘模型中，NMU缺陷小鼠的气道嗜酸性粒细胞增多减少。野生型和NMU敲除小鼠之间抗原诱导的Th 2应答没有差异。NMU-R1在嗜酸性粒细胞系中高度表达，并且NMU直接诱导Ca 2+动员和细胞外/信号调节激酶磷酸化。NMU还诱导细胞粘附到细胞外基质（纤连蛋白和I型胶原蛋白）的组分，并在体外趋化。此外，NMU-R1也在人外周血嗜酸性粒细胞中表达，并且NMU以剂量依赖性方式诱导细胞粘附。这些数据表明，NMU通过直接激活嗜酸性粒细胞促进嗜酸性粒细胞浸润到炎症部位。我们的研究表明，NMU受体拮抗剂可能是药物抑制过敏性炎症性疾病，包括哮喘的新目标。
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.