Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Neuroscience Research Center of Changzheng Hospital, Second Military Medical University, Shanghai, China.
Glia. 2013 Apr;61(4):490-503. doi: 10.1002/glia.22450. Epub 2013 Jan 22.
The olfactory system is an unusual tissue in which olfactory receptor neurons (ORNs) are continuously replaced throughout the life of mammals. Clearance of the apoptotic ORNs corpses is a fundamental process serving important functions in the regulation of olfactory nerve turnover and regeneration. However, little is known about the underlying mechanisms. Olfactory ensheathing cells (OECs) are a unique type of glial cells that wrap olfactory axons and support their continual regeneration from the olfactory epithelium to the bulb. In the present study, OECs were identified to exist in two different states, resting and reactive, in which resting OECs could be activated by LPS stimulation and functioned as phagocytes for cleaning apoptotic ORNs corpses. Confocal analysis revealed that dead ORNs debris were engulfed by OECs and co-localized with lysosome associated membrane protein 1. Moreover, phosphatidylserine (PS) receptor was identified to express on OECs, which allowed OECs to recognize apoptotic ORNs by binding to PS. Importantly, engulfment of olfactory nerve debris by OECs was found in olfactory mucosa under normal turnover and was significantly increased in the animal model of olfactory bulbectomy, while little phagocytosis by Iba-1-positive microglia/macrophages was observed. Together, these results implicate OEC as a primary innate immunocyte in the olfactory pathway, and suggest a cellular and molecular mechanism by which ORNs corpses are removed during olfactory nerve turnover and regeneration.
嗅觉系统是一种特殊的组织，在哺乳动物的整个生命周期中，嗅觉受体神经元（ORNs）不断被替换。清除凋亡的 ORN 尸体是一个基本过程，在调节嗅神经更替和再生中起着重要作用。然而，其潜在机制知之甚少。嗅鞘细胞（OECs）是一种独特的神经胶质细胞，它包裹着嗅神经轴突，并支持它们从嗅上皮持续再生到嗅球。在本研究中，鉴定出 OECs 存在两种不同的状态，静息和反应状态，其中静息 OECs 可以被 LPS 刺激激活，并作为吞噬细胞清除凋亡的 ORN 尸体。共聚焦分析显示，死亡的 ORN 碎片被 OECs 吞噬，并与溶酶体相关膜蛋白 1 共定位。此外，还鉴定出 PS 受体在 OECs 上表达，这使得 OECs 能够通过与 PS 结合来识别凋亡的 ORN。重要的是，在正常更替的嗅黏膜中发现 OECs 吞噬嗅神经碎片，在嗅球切除术的动物模型中则明显增加，而小胶质细胞/巨噬细胞的 Iba-1 阳性吞噬作用则很少观察到。总之，这些结果表明 OEC 是嗅觉通路中的主要固有免疫细胞，并提示了一种细胞和分子机制，通过该机制，在嗅神经更替和再生过程中清除 ORN 尸体。
