Acute injury in the peripheral nervous system triggers an alternative macrophage response.
Acute injury in the peripheral nervous system triggers an alternative macrophage response.
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DOI：
10.1186/1742-2094-9-176
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发表时间：
2012-07-20
影响因子：
9.3
通讯作者：
Janssens S
中科院分区：
文献类型：
--
作者：
Ydens E;Cauwels A;Asselbergh B;Goethals S;Peeraer L;Lornet G;Almeida-Souza L;Van Ginderachter JA;Timmerman V;Janssens S
神经退行性变中免疫系统的激活具有有害和有益的影响。这种免疫反应的哪些方面加剧了神经退行性崩溃，哪些方面刺激了再生仍然是一个悬而未决的问题。为了阐明免疫系统的神经保护作用，我们将重点放在急性周围神经损伤模型上，其中免疫系统显示出保护作用。为了确定坐骨神经（周围神经系统沃勒变性模型）轴突切断后触发的免疫应答类型，我们使用实时定量聚合酶链反应（RT-qPCR）、蛋白质印迹和免疫组织化学评价了代表I型和II型免疫应答（经典与替代）两种极端的标志物。我们的研究结果表明，急性周围神经损伤触发抗炎和免疫抑制反应，而不是促炎反应。这反映在经典巨噬细胞标志物（iNOS、IFNγ和IL 12 p40）的完全缺失以及组织修复标志物（iNOS-1、Ym 1和Trem 2）的强烈上调。有利于替代巨噬细胞环境的信号在神经损伤后立即被诱导，并且似乎在巨噬细胞浸润之前在神经内建立。此外，诱导先天免疫应答的负调节因子以及抗炎细胞因子IL-10。免疫系统的严格调节抑制了过度激活反应的潜在组织损伤作用。我们在这里证明，急性周围神经损伤触发一个固有的保护环境，诱导M2表型的巨噬细胞和表达的巨噬细胞-1。我们认为，M2表型，与无菌炎症反应和组织修复，可能解释他们的神经保护能力。因此，将神经变性诱导的免疫应答向M2/Th 2应答转变可能是重要的治疗策略。
The activation of the immune system in neurodegeneration has detrimental as well as beneficial effects. Which aspects of this immune response aggravate the neurodegenerative breakdown and which stimulate regeneration remains an open question. To unravel the neuroprotective aspects of the immune system we focused on a model of acute peripheral nerve injury, in which the immune system was shown to be protective. To determine the type of immune response triggered after axotomy of the sciatic nerve, a model for Wallerian degeneration in the peripheral nervous system, we evaluated markers representing the two extremes of a type I and type II immune response (classical vs. alternative) using real-time quantitative polymerase chain reaction (RT-qPCR), western blot, and immunohistochemistry. Our results showed that acute peripheral nerve injury triggers an anti-inflammatory and immunosuppressive response, rather than a pro-inflammatory response. This was reflected by the complete absence of classical macrophage markers (iNOS, IFNγ, and IL12p40), and the strong up-regulation of tissue repair markers (arginase-1, Ym1, and Trem2). The signal favoring the alternative macrophage environment was induced immediately after nerve damage and appeared to be established within the nerve, well before the infiltration of macrophages. In addition, negative regulators of the innate immune response, as well as the anti-inflammatory cytokine IL-10 were induced. The strict regulation of the immune system dampens the potential tissue damaging effects of an over-activated response. We here demonstrate that acute peripheral nerve injury triggers an inherent protective environment by inducing the M2 phenotype of macrophages and the expression of arginase-1. We believe that the M2 phenotype, associated with a sterile inflammatory response and tissue repair, might explain their neuroprotective capacity. As such, shifting the neurodegeneration-induced immune responses towards an M2/Th2 response could be an important therapeutic strategy.
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影响因子：
4.4
作者：
Dahle, C;Ekerfelt, C;Ernerudh, J
通讯作者：
Ernerudh, J
影响因子：
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作者：
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Seaman, WE
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作者：
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通讯作者：
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影响因子：
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作者：
Boone, DL;Turer, EE;Ma, A
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