The neuropeptide neuromedin U promotes inflammation by direct activation of mast cells.
The neuropeptide neuromedin U promotes inflammation by direct activation of mast cells.
复制标题
DOI：
10.1084/jem.20050248
复制
发表时间：
2005-07-18
影响因子：
15.3
通讯作者：
Kojima, Masayasu
中科院分区：
文献类型：
--
作者：
Moriyama, Maiko;Sato, Takahiro;Inoue, Hiromasa;Fukuyama, Satoru;Teranishi, Hitoshi;Kangawa, Kenji;Kano, Tatsuhiko;Yoshimura, Akihiko;Kojima, Masayasu
神经梅毒素U(NMU)是一种在胃肠道和中枢神经系统表达的神经肽。NMU与两个G蛋白偶联受体NMU-R1和NMU-R2相互作用。NMU-R2主要定位于神经细胞，而NMU-R1表达于外周组织，包括淋巴细胞和单核细胞，提示NMU在免疫调节中发挥作用。然而，NMU在外周组织中的功能尚不清楚。在这项研究中，利用NMU缺陷小鼠，我们首先证明了NMU在肥大细胞介导的炎症中起着重要作用。在肥大细胞缺陷的WBB6F1-W/W v小鼠中，完全弗氏佐剂诱导的肥大细胞脱颗粒以及水肿和中性粒细胞浸润在NMU缺陷小鼠中没有发生。此外，足底注射NMU可引起WT小鼠早期炎症反应，如肥大细胞脱颗粒、血管扩张和血浆外渗，而WBB6F1-W/Wv小鼠则无此反应。NMU-R1在原代培养的肥大细胞中高表达，NMU可诱导腹膜肥大细胞内钙离子动员和脱颗粒。这些数据表明，NMU促进肥大细胞介导的炎症；因此，NMU受体拮抗剂可能成为药物抑制肥大细胞介导的炎症性疾病的新靶点。
Neuromedin U (NMU) is a neuropeptide that is expressed in the gastrointestinal tract and central nervous system. NMU interacts with two G protein–coupled receptors, NMU-R1 and NMU-R2. Whereas NMU-R2 localizes predominantly to nerve cells, NMU-R1 is expressed in peripheral tissues including lymphocytes and monocytes, suggesting a role of NMU in immunoregulation. However, the functions of NMU in peripheral tissues have not been clarified. In this study, using NMU-deficient mice, we first demonstrated that NMU plays an important role in mast cell-mediated inflammation. Complete Freund's adjuvant-induced mast cell degranulation as well as edema and neutrophil infiltration, which occurred weakly in mast cell–deficient WBB6F1-W/W v mice, did not occur in NMU-deficient mice. Moreover, intraplantar injection of NMU into paws induced early inflammatory responses such as mast cell degranulation, vasodilation, and plasma extravasation in WT mice but not in WBB6F1-W/W v mice. NMU-R1 was highly expressed in primary mast cells, and NMU induced Ca2+ mobilization and degranulation in peritoneal mast cells. These data indicate that NMU promotes mast cell–mediated inflammation; therefore, NMU receptor antagonists could be a novel target for pharmacological inhibition of mast cell–mediated inflammatory diseases.