Be'eri H, Reichert F, Saada A, Rotshenker S
Department of Anatomy & Cell Biology, Hebrew University-Hadassah Medical School, POB 12272, Jerusalem 91120, Israel.
Eur J Neurosci. 1998 Aug;10(8):2707-13.
Wallerian degeneration (WD) is the inflammatory response of peripheral nerves to injury. Evidence is provided that granulocyte macrophage colony stimulating factor (GM-CSF) contributes to the initiation and progression of WD by activating macrophages and Schwann, whereas IL-10 down-regulates WD by inhibiting GM-CSF production. A significant role of activated macrophages and Schwann for future regeneration is myelin removal by phagocytosis and degradation. We studied the timing and magnitude of GM-CSF and IL-10 production, macrophage and Schwann activation, and myelin degradation in C57BL/6NHSD and C57BL/6-WLD/OLA/NHSD mice that display normal rapid-WD and abnormal slow-WD, respectively. We observed the following events in rapid-WD. The onset of GM-CSF production is within 5 h after injury. Production is steadily augmented during the first 3 days, but is attenuated thereafter. The onset of production of the macrophage and Schwann activation marker Galectin-3/MAC-2 succeeds that of GM-CSF. Galectin-3/MAC-2 production is up-regulated during the first 6 days, but is down-regulated thereafter. The onset of myelin degradation succeeds that of Galectin-3/MAC-2, and is almost complete within 1 week. IL-10 production displays two phases. An immediate low followed by a high that begins on the fourth day, reaching highest levels on the seventh. The timing and magnitude of GM-CSF production thus enable the rapid activation of macrophages and Schwann that consequently phagocytose and degrade myelin. The timing and magnitude of IL-10 production suggest a role in down-regulating WD after myelin is removed. In contrast, slow-WD nerves produce low inefficient levels of GM-CSF and IL-10 throughout. Therefore, deficient IL-10 levels cannot account for inefficient GM-CSF production, whereas deficient GM-CSF levels may account, in part, for slow-WD.
沃勒变性（WD）是外周神经对损伤的炎症反应。有证据表明，粒细胞巨噬细胞集落刺激因子（GM-CSF）通过激活巨噬细胞和施万细胞促进WD的起始和进展，而白细胞介素-10（IL-10）通过抑制GM-CSF的产生下调WD。活化的巨噬细胞和施万细胞对未来再生的一个重要作用是通过吞噬作用和降解来清除髓鞘。我们研究了C57BL/6NHSD和C57BL/6-WLD/OLA/NHSD小鼠中GM-CSF和IL-10产生的时间和幅度、巨噬细胞和施万细胞的活化以及髓鞘降解情况，这两种小鼠分别表现出正常的快速WD和异常的缓慢WD。我们在快速WD中观察到以下事件。GM-CSF的产生在损伤后5小时内开始。在最初3天内产量稳步增加，但此后减弱。巨噬细胞和施万细胞活化标志物半乳糖凝集素-3/MAC-2的产生起始时间在GM-CSF之后。半乳糖凝集素-3/MAC-2的产生在最初6天内上调，但此后下调。髓鞘降解的起始时间在半乳糖凝集素-3/MAC-2之后，并且在1周内几乎完成。IL-10的产生呈现两个阶段。先是立即出现低水平，随后在第四天开始出现高水平，在第七天达到最高水平。GM-CSF产生的时间和幅度因此能够使巨噬细胞和施万细胞迅速活化，从而吞噬和降解髓鞘。IL-10产生的时间和幅度表明其在髓鞘被清除后下调WD中发挥作用。相比之下，缓慢WD神经始终产生低效水平的GM-CSF和IL-10。因此，IL-10水平不足不能解释GM-CSF产生效率低下的问题，而GM-CSF水平不足可能部分解释了缓慢WD的原因。
