Involvement of monocyte chemoattractant protein-1, macrophage inflammatory protein-1α and interleukin-1β in Wallerian degeneration
Involvement of monocyte chemoattractant protein-1, macrophage inflammatory protein-1α and interleukin-1β in Wallerian degeneration
复制标题
DOI：
10.1093/brain/awh407
复制
发表时间：
2005-04-01
期刊：
影响因子：
14.5
通讯作者：
David, S
中科院分区：
文献类型：
--
作者：
Perrin, FE;Lacroix, S;David, S
CNS和PNS中的沃勒变性由轴突及其损伤部位远端的髓鞘的降解和吞噬作用组成。这种变性过程需要有效的巨噬细胞反应，在外周神经中迅速发生，但在CNS中缓慢。周围神经的快速沃勒变性可能有助于随后的轴突再生。我们发现，有一个显着增加的mRNA表达的三个促炎分子，趋化因子单核细胞趋化蛋白-1（MCP-1）和巨噬细胞炎症蛋白-1 α（MIP-1 α），和细胞因子白细胞介素-1 β（IL-1 β），在小鼠坐骨神经，但不是在脊髓进行沃勒变性。用功能阻断抗体中和受损坐骨神经中的MCP-1、MIP-1 α和IL-1 β可抑制巨噬细胞反应和髓鞘清除。将重组MCP-1、MIP-1 α或IL-1 β注射到正常、未损伤的脊髓中，触发了许多趋化因子和细胞因子的表达。此外，将重组MCP-1/MIP-1 α或IL-1 β注射到经历Wallerian变性的脊髓背柱中触发了快速的巨噬细胞/小胶质细胞活化和髓鞘清除。这些发现提供了直接证据，表明MCP-1、MIP-1 α和IL-1 β是导致沃勒变性中髓鞘快速分解和清除的巨噬细胞反应的重要调节剂。
Wallerian degeneration in the CNS and PNS consists of degradation and phagocytosis of axons and their myelin sheath distal to the site of injury. This process of degeneration, which requires an effective macrophage response, occurs rapidly in peripheral nerves but is slow in the CNS. Rapid Wallerian degeneration in peripheral nerves may contribute to subsequent axonal regeneration. We show that there is a marked increase in mRNA expression of three pro-inflammatory molecules, the chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 alpha (MIP-1 alpha), and the cytokine interleukin-1 beta (IL-1 beta), in the mouse sciatic nerve but not in the spinal cord undergoing Wallerian degeneration. Neutralizing MCP-1, MIP-1 alpha and IL-1 beta in the lesioned sciatic nerve with function-blocking antibodies suppressed macrophage responses and myelin clearance. Injecting recombinant MCP-1, MIP-1 alpha or IL-1 beta into the normal, uninjured spinal cord triggered the expression of a number of chemokines and cytokines. Furthermore, injecting recombinant MCP-1/MIP-1 alpha or IL-1 beta into the dorsal column of the spinal cord undergoing Wallerian degeneration triggered rapid macrophage/microglial activation and myelin clearance. These findings provide direct evidence that MCP-1, MIP-1 alpha and IL-1 beta are important regulators of macrophage responses that lead to rapid myelin breakdown and clearance in Wallerian degeneration.