外周神经损伤后,CXCR2 介导的中性粒细胞转运和中性粒细胞细胞外陷阱对于髓鞘清除是必需的。
CXCR2 mediated trafficking of neutrophils and neutrophil extracellular traps are required for myelin clearance after a peripheral nerve injury.
机构信息
Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4975, USA.
Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4975, USA.
出版信息
Exp Neurol. 2024 Dec;382:114985. doi: 10.1016/j.expneurol.2024.114985. Epub 2024 Oct 3.
Neutrophils are a vital part of the innate immune system. Many of their functions eliminate bacteria & viruses, like neutrophil extracellular traps (NETs), which trap bacteria, enhancing macrophage phagocytosis. It was surprising when it was demonstrated that neutrophils are a part of Wallerian degeneration, a process that is essential for nerve regeneration after a nerve injury. It is not known what signals attract neutrophils into the nerve and how they aid Wallerian degeneration. Neutrophils accumulate in the distal nerve within one day after an injury and are found in the nerve from one to three days. We demonstrate that CXCR2 mediates the trafficking of neutrophils into the distal nerve, and without CXCR2 Wallerian degeneration, as indicated by luxol fast blue staining, was reduced seven days after a sciatic nerve crush or transection injury. NETs were detected in the distal nerve after a sciatic nerve transection. NET formation has been shown to require protein arginine deiminase 4 (PAD4), which citrullinates histone 3. Inhibiting PAD4 reduced NET formation significantly in the distal nerve at two days and myelin clearance at seven days indicating that NETs aid myelin clearance. These results demonstrate another function for NETs other than clearing pathogens. Neutrophils have been detected after injuries to the central nervous system and diseases in humans and animal models. Our results demonstrate neutrophils aid myelin clearance, suggesting a role for their presence in central nervous system injuries and diseases.
中性粒细胞是先天免疫系统的重要组成部分。它们的许多功能可以消除细菌和病毒,如中性粒细胞胞外诱捕网(NETs),它可以捕获细菌,增强巨噬细胞的吞噬作用。令人惊讶的是,中性粒细胞是 Wallerian 变性的一部分,这是神经损伤后神经再生所必需的过程。目前还不清楚是什么信号吸引中性粒细胞进入神经,以及它们如何帮助 Wallerian 变性。损伤后一天,中性粒细胞就在远端神经中积聚,并在神经中存在 1 到 3 天。我们证明,CXCR2 介导中性粒细胞向远端神经的迁移,而缺乏 CXCR2 的 Wallerian 变性,如卢索快速蓝染色所示,在坐骨神经挤压或横断损伤后 7 天减少。在坐骨神经横断后,在远端神经中检测到 NETs。已经表明 NET 的形成需要蛋白精氨酸脱亚氨酶 4(PAD4),它使组蛋白 3 瓜氨酸化。抑制 PAD4 在两天时显著减少了远端神经中的 NET 形成,并且在 7 天时减少了髓鞘清除,表明 NETs 有助于髓鞘清除。这些结果表明 NET 除了清除病原体外还有另一种功能。在人类和动物模型的中枢神经系统损伤和疾病中已经检测到中性粒细胞。我们的结果表明中性粒细胞有助于髓鞘清除,这表明它们在中枢神经系统损伤和疾病中的存在具有一定作用。
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