Matsumoto Y, Ohmori K, Fujiwara M
Department of Immunology, Niigata University School of Medicine, Japan.
J Neuroimmunol. 1992 Mar;37(1-2):23-33. doi: 10.1016/0165-5728(92)90152-b.
Gliosis is a repair process of lesions appearing in the central nervous system (CNS). Although gliosis by astrocytes (astrocytic gliosis) has been well documented, that by microglia (microglial gliosis) remains poorly understood. In the present study we induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats and examined microglial and astroglial reactions to EAE lesions at various stages of the disease by immunohistochemistry. For the demonstration of microglia and astrocytes, antibodies against complement receptor type 3 (OX42) and glial fibrillary acidic protein (GFAP) were used, respectively. It was revealed that the whole course of microglial and astroglial reactions to EAE lesions is divisible into three stages, i.e., initial, peak and recovery stages. Microglial and astroglial reactions to EAE lesions at each stage correspond well with the clinical and histological stages of EAE. At the initial stage, rats showed mild clinical signs and a few inflammatory foci were found in the CNS. Microglia were increased in number in close association with inflammatory cell aggregates, whereas astrocytes showed no significant reaction in spite of the presence of inflammatory cells. At the peak stage, rats showed full-blown EAE and the number of inflammatory cells reached maximum. The most characteristic finding at this stage was 'encasement' of inflammatory lesions by astrocytic fibers. Microglia were increased in number, but association of microglia with lesions was prevented by astrocytes. Interestingly, however, such characteristic distribution of microglia and astrocytes was not observed at the recovery stage. Residual inflammatory cell aggregates were intermingled with dense microglial and astrocytic gliosis, forming 'micro-astroglial scars'. Double immunofluorescence staining with anti-GFAP and anti-bromodeoxyuridine (BrdU), or with OX42 and anti-BrdU revealed that BrdU-incorporated microglia, but not astrocytes, were present mainly at the initial and peak stages, suggesting that microglia would proliferate by cell division to create gliosis, whereas astrocytic gliosis would be a result of migration of astrocytes and/or up-regulation of expression of GFAP molecule. Taken together with previous in vitro findings that microglia, but not astrocytes, stimulate encephalitogenic T cell proliferation, these in vivo findings suggest that microglia augment, whereas astrocytes suppress, inflammatory processes in the CNS.
胶质增生是中枢神经系统（CNS）中出现的损伤的修复过程。虽然星形胶质细胞引起的胶质增生（星形细胞胶质增生）已有充分记载，但小胶质细胞引起的胶质增生（小胶质细胞胶质增生）仍了解甚少。在本研究中，我们在Lewis大鼠中诱导实验性自身免疫性脑脊髓炎（EAE），并通过免疫组织化学检查疾病不同阶段小胶质细胞和星形胶质细胞对EAE损伤的反应。为了显示小胶质细胞和星形胶质细胞，分别使用了抗补体受体3（OX42）抗体和胶质纤维酸性蛋白（GFAP）抗体。结果表明，小胶质细胞和星形胶质细胞对EAE损伤的整个过程可分为三个阶段，即初始阶段、高峰期和恢复期。每个阶段小胶质细胞和星形胶质细胞对EAE损伤的反应与EAE的临床和组织学阶段密切相关。在初始阶段，大鼠表现出轻微的临床症状，在CNS中发现了一些炎症病灶。小胶质细胞数量增加，与炎性细胞聚集密切相关，而星形胶质细胞尽管存在炎性细胞，但未表现出明显反应。在高峰期，大鼠表现出典型的EAE，炎性细胞数量达到最大值。此阶段最具特征性的发现是星形胶质纤维对炎性病灶的“包裹”。小胶质细胞数量增加，但星形胶质细胞阻止了小胶质细胞与病灶的关联。然而，有趣的是，在恢复期未观察到小胶质细胞和星形胶质细胞的这种特征性分布。残留的炎性细胞聚集与密集的小胶质细胞和星形细胞胶质增生混合在一起，形成“小胶质-星形细胞瘢痕”。用抗GFAP和抗溴脱氧尿苷（BrdU）或用OX42和抗BrdU进行双重免疫荧光染色显示，掺入BrdU的小胶质细胞而非星形胶质细胞主要存在于初始阶段和高峰期，这表明小胶质细胞会通过细胞分裂增殖以形成胶质增生，而星形细胞胶质增生将是星形胶质细胞迁移和/或GFAP分子表达上调的结果。结合先前的体外研究结果，即小胶质细胞而非星形胶质细胞刺激致脑炎性T细胞增殖，这些体内研究结果表明，小胶质细胞增强而星形胶质细胞抑制CNS中的炎症过程。
