Neutrophils Are Critical for Myelin Removal in a Peripheral Nerve Injury Model of Wallerian Degeneration

被引:141
作者
Lindborg, Jane A. [1 ]
Mack, Matthias [2 ]
Zigmond, Richard E. [1 ]
机构
[1] Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USA
[2] Univ Hosp Regensburg, Dept Internal Med 2, D-93053 Regensburg, Germany
基金
美国国家卫生研究院;
关键词
axotomy; macrophages; neutrophils; phagocytosis; sciatic nerve; Wallerian degeneration; MONOCYTE CHEMOATTRACTANT PROTEIN-1; MACROPHAGE RECRUITMENT; APOPTOTIC NEUTROPHILS; CHEMOKINE RECEPTOR; SCHWANN-CELLS; AXONAL DEGENERATION; FUNCTIONAL RECOVERY; GRANULE DEFICIENCY; NEUROPATHIC PAIN; BLOOD MONOCYTES;
D O I
10.1523/JNEUROSCI.2085-17.2017
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Wallerian degeneration (WD) is considered an essential preparatory stage to the process of axonal regeneration. In the peripheral nervous system, infiltrating monocyte-derived macrophages, which use the chemokine receptor CCR2 to gain entry to injured tissues from the bloodstream, are purportedly necessary for efficient WD. However, our laboratory has previously reported that myelin clearance in the injured sciatic nerve proceeds unhindered in the Ccr2(-/-) mouse model. Here, we extensively characterize WD in male Ccr2(-/-) mice and identify a compensatory mechanism of WD that is facilitated primarily by neutrophils. In response to the loss of CCR2, injured Ccr2(-/-) sciatic nerves demonstrate prolonged expression of neutrophil chemokines, a concomitant extended increase in the accumulation of neutrophils in the nerve, and elevated phagocytosis by neutrophils. Neutrophil depletion substantially inhibits myelin clearance after nerve injury in both male WT and Ccr2(-/-) mice, highlighting a novel role for these cells in peripheral nerve degeneration that spans genotypes.
引用
收藏
页码:10258 / 10277
页数:20
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