Liu H M, Yang L H, Yang Y J
Department of Pathology, National Cheng Kung University, Medical College, Tainan, Taiwan, R.O.C.
J Neuropathol Exp Neurol. 1995 Jul;54(4):487-96.
The role of Schwann cells (SC) during Wallerian degeneration has been controversial. The consensus opinion is that monocytes/macrophages are mainly responsible for myelin removal although SC were shown to phagocytose myelin in vitro and in vivo. In the present study, we correlate proto-oncogene expression with phenotypic changes in SC during Wallerian degeneration using immunohistochemistry and electron microscopy. The proliferative cells are labeled with proliferative cell nuclear antigen (PCNA), and macrophages are labeled with ED1 macrophage marker. We demonstrate c-fos expression in SC at the onset of axon disintegration 12 hours post-axotomy followed by expression of ED1, basic fibroblast growth factor (bFGF) and PCNA after 1 day. The myelin sheath fragments at the nodal region and forms ellipsoids. Schwann cells move to internodes and undergo nuclear and cytoplasmic hypertrophy; they phagocytose myelin ellipsoids with thick vimentin-rich processes and undergo mitosis. Resident macrophages express c-fos and phagocytose myelin debris sequestered into endoneurium by SC after 3 days, but they do not enter the tube until the fifth day. We believe that SC are induced by signals from injured axons to express c-fos which activates downstream genes that lead to the acquisition of phagocytic and proliferative activities. Myelin debris processed by SC may act as an inducer and a chemoattractant for resident macrophages. Cytokines produced by macrophages may stimulate SC proliferation and production of neurotrophic factors.
施万细胞（SC）在沃勒变性过程中的作用一直存在争议。目前的共识观点是，单核细胞/巨噬细胞主要负责髓鞘清除，尽管在体外和体内研究均显示施万细胞能够吞噬髓鞘。在本研究中，我们运用免疫组织化学和电子显微镜技术，将原癌基因表达与沃勒变性过程中施万细胞的表型变化相关联。增殖细胞用增殖细胞核抗原（PCNA）标记，巨噬细胞用ED1巨噬细胞标志物标记。我们发现，在轴突切断后12小时轴突崩解开始时，施万细胞中有c-fos表达，随后在1天后出现ED1、碱性成纤维细胞生长因子（bFGF）和PCNA的表达。髓鞘在结区断裂并形成椭圆形。施万细胞迁移至节间并发生核与胞质肥大；它们通过富含波形蛋白且粗大的突起吞噬髓鞘椭圆形结构，并进行有丝分裂。驻留巨噬细胞在3天后表达c-fos并吞噬由施万细胞隔离至神经内膜的髓鞘碎片，但直到第5天才进入神经纤维管。我们认为，施万细胞受损伤轴突发出的信号诱导而表达c-fos，c-fos激活下游基因，进而导致施万细胞获得吞噬和增殖活性。施万细胞处理的髓鞘碎片可能作为驻留巨噬细胞的诱导剂和趋化因子。巨噬细胞产生的细胞因子可能刺激施万细胞增殖并产生神经营养因子。
