Olfactory ensheathing cells: The primary innate immunocytes in the olfactory pathway to engulf apoptotic olfactory nerve debris
Olfactory ensheathing cells: The primary innate immunocytes in the olfactory pathway to engulf apoptotic olfactory nerve debris
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嗅鞘细胞：嗅觉通路中吞噬凋亡嗅神经碎片的主要先天免疫细胞
作者：
Su, Zhida;Chen, Jingjing;He, Cheng
嗅觉系统是一种特殊的组织，在哺乳动物的一生中，嗅觉受体神经元（ORN）不断地被替换。清除凋亡的ORN尸体是一个基本的过程，在嗅觉神经的更新和再生的调节中发挥重要作用。然而，人们对潜在的机制知之甚少。嗅鞘细胞（OECs）是一种独特的神经胶质细胞，它包裹着嗅轴突，并支持嗅轴突从嗅上皮到嗅球的持续再生。在本研究中，OECs被鉴定为存在于两种不同的状态，静息和反应性，其中静息OECs可以被LPS刺激激活，并作为吞噬细胞用于清洁凋亡的ORN尸体。共聚焦分析显示，死亡的ORN碎片被OEC吞噬，并与溶酶体相关膜蛋白1共定位。此外，磷脂酰丝氨酸（PS）受体被鉴定为在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，嗅鞘细胞对嗅神经碎片的吞噬作用在正常转换的嗅粘膜中发现，并且在嗅球切除术的动物模型中显著增加，而Iba‐1阳性小胶质细胞/巨噬细胞的吞噬作用很小。总之，这些结果暗示OEC作为嗅觉通路中的主要先天免疫细胞，并表明在嗅觉神经周转和再生过程中ORN尸体被去除的细胞和分子机制。© 2013 Wiley Periodicals，Inc.
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. © 2013 Wiley Periodicals, Inc.