The guidance receptor neogenin promotes pulmonary inflammation during lung injury
The guidance receptor neogenin promotes pulmonary inflammation during lung injury
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DOI：
10.1096/fj.11-200063
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发表时间：
2012-04-01
期刊：
影响因子：
4.8
通讯作者：
Rosenberger, Peter
中科院分区：
文献类型：
--
作者：
Mirakaj, Valbona;Jennewein, Carla;Rosenberger, Peter
肺损伤的特征是肺组织内持续的自蔓延炎症，其由白细胞迁移到肺泡腔中引发。最近的工作表明，神经元的指导蛋白参与白细胞迁移的编排。再生蛋白是轴突迁移的重要指导受体，但其在白细胞迁移和急性炎症中的作用迄今尚不清楚。在这里，我们报告说，再生蛋白影响中性粒细胞迁移通过内皮细胞HMEC-1和肺泡A549单层在体外。在体内，Neo 1（-/-）小鼠在肺损伤期间表现出肺泡腔内细胞计数减少59%，TNF-α减少41%，IL-6水平减少76%。在使用嵌合体动物的研究中，Neo 1（-/-）骨髓的存在与肺损伤期间肺组织内细胞计数减少42%和炎性变化减少相关。通过抗体注射再生蛋白的功能抑制证实了这些结果和再生蛋白在肺泡腔内的炎症变化中的作用。以前未被认识到，指导受体再生蛋白对白细胞迁移的编排和急性炎症的控制具有显着影响。Mirakaj，V.，Jennewein，C.，Konig，K.，Granja，T.，Rosenberger，P.指导受体再生蛋白在肺损伤期间促进肺部炎症。FASEB J.26，1549-1558（2012）。www.fasebj.org
Lung injury is marked by a persistent self-propagating inflammation within the pulmonary tissue that is initiated by the migration of leukocytes into the alveolar space. Recent work has demonstrated that neuronal guidance proteins are involved into the orchestration of leukocyte migration. Neogenin is a crucial guidance receptor for axonal migration, yet its role during leukocyte migration and acute inflammation is to date unknown. Here, we report that neogenin influences neutrophil migration across endothelial HMEC-1 and alveolar A549 monolayers in vitro. In vivo, Neo1(-/-) mice demonstrated 59% reduced cell count, 41% reduced TNF-alpha, and 76% reduced IL-6 levels within the alveolar space during lung injury. In studies employing chimeric animals, the presence of Neo1(-/-) bone marrow was associated with a 42% reduction of cell count and reduced inflammatory changes within pulmonary tissue during lung injury. The functional inhibition of neogenin through antibody injection confirmed these results and the role of neogenin for the inflammatory changes within the alveolar space. Previously unappreciated, the guidance receptor neogenin has a significant effect on the orchestration of leukocyte migration and the control of acute inflammation.-Mirakaj, V., Jennewein, C., Konig, K., Granja, T., Rosenberger, P. The guidance receptor neogenin promotes pulmonary inflammation during lung injury. FASEB J. 26, 1549-1558 (2012). www.fasebj.org