The chemokine receptor CCR2 is involved in macrophage recruitment to the injured peripheral nervous system
The chemokine receptor CCR2 is involved in macrophage recruitment to the injured peripheral nervous system
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DOI：
10.1016/s0165-5728(00)00343-x
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发表时间：
2000-10-02
影响因子：
3.3
通讯作者：
Brück, W
中科院分区：
文献类型：
--
作者：
Siebert, H;Sachse, A;Brück, W
沃勒氏变性是神经系统轴突横断后最基本的反应之一，导致从体循环中募集单个核细胞。然而，调控这种细胞入侵的确切机制尚未被详细阐明。趋化因子及其受体在白细胞运输中起着核心作用，特别是趋化因子MCP-1在巨噬细胞向受损神经系统募集中起着重要作用。本研究研究了两种趋化因子受体缺失的小鼠坐骨神经横断后的Wallerian变性过程：CCR2是MCP-1的主要受体，CCR5是Th1 T淋巴细胞的标记物，但也存在于巨噬细胞中。通过免疫细胞化学检测三种典型巨噬细胞抗原（F4/80、Mac-1、LFA-1）的侵袭性巨噬细胞数量。趋化因子受体CCR2在横断的神经残端通过浸润细胞表达。与野生型对照和ccr5缺失小鼠相比，ccr2敲除小鼠的巨噬细胞侵袭明显受损。随后，由于吞噬巨噬细胞侵袭减少，髓磷脂吞噬相应减少。这些数据表明趋化因子受体CCR2参与巨噬细胞向受损神经系统的募集。(C) 2000 Elsevier Science B.V.版权所有
Wallerian degeneration is one of the most elementary reactions of the nervous system after transection of axons, leading to the recruitment of mononuclear cells from the systemic circulation. However, the exact mechanisms regulating this cell invasion have not yet been clarified in detail. Chemokines and their receptors play a central role in leukocyte trafficking, in particular the chemokine MCP-1 has been strongly implicated in macrophage recruitment to the injured nervous system. The present study investigates the course of Wallerian degeneration after transection of the sciatic nerve in mice deficient in two chemokine receptors: CCR2, the main receptor for MCP-1, and CCR5, a marker for Th1 T lymphocytes but also present on macrophages. The number of invading macrophages was determined by immunocytochemistry for three typical macrophage antigens (F4/80, Mac-1, LFA-1). The chemokine receptor CCR2 was expressed by infiltrating cells in the transected nerve stumps. Macrophage invasion was significantly impaired in CCR2-knockout mice when compared with wildtype controls and CCR5-deficient mice. Subsequently, there was a corresponding decrease in myelin phagocytosis due to the reduced invasion of phagocytic macrophages. These data demonstrate the involvement of the chemokine receptor CCR2 in macrophage recruitment to the injured nervous system. (C) 2000 Elsevier Science B.V. All rights reserved.