MICROGLIAL AND ASTROGLIAL REACTIONS TO INFLAMMATORY LESIONS OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN THE RAT CENTRAL-NERVOUS-SYSTEM
MICROGLIAL AND ASTROGLIAL REACTIONS TO INFLAMMATORY LESIONS OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN THE RAT CENTRAL-NERVOUS-SYSTEM
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DOI：
10.1016/0165-5728(92)90152-b
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发表时间：
1992-03-01
影响因子：
3.3
通讯作者：
FUJIWARA, M
中科院分区：
文献类型：
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作者：
MATSUMOTO, Y;OHMORI, K;FUJIWARA, M
胶质增生症是出现在中枢神经系统(CNS)的损伤的修复过程。虽然星形胶质细胞引起的胶质细胞增生症(星形细胞胶质细胞增生症)已有很好的文献记载，但由小胶质细胞引起的胶质细胞增生症(小胶质细胞增生症)仍然知之甚少。在本研究中，我们诱导了Lewis大鼠实验性自身免疫性脑脊髓炎(EAE)，并用免疫组织化学方法检测了疾病不同阶段的小胶质细胞和星形胶质细胞对EAE病变的反应。小胶质细胞和星形胶质细胞分别用补体受体3型(OX42)和胶质纤维酸性蛋白(GFAP)抗体显示。结果表明，小胶质细胞和星形胶质细胞对EAE损伤反应的全过程可分为三个阶段，即初期、高峰期和恢复期。每一阶段的小胶质细胞和星形胶质细胞对EAE损害的反应与EAE的临床和组织学分期相一致。早期大鼠临床症状轻微，中枢神经系统可见少量炎性灶。小胶质细胞数量增多，与炎性细胞聚集密切相关，而星形胶质细胞虽有炎性细胞，但无明显反应。在高峰期，大鼠出现全面的EAE，炎性细胞数量达到最大。这一阶段最具特征的发现是星形细胞纤维包裹炎性病变。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变的联系。然而，有趣的是，在恢复期没有观察到小胶质细胞和星形胶质细胞的这种特征分布。残留的炎性细胞聚集体与致密的小胶质细胞和星形胶质细胞混杂在一起，形成“微小星形胶质细胞瘢痕”。抗GFAP和抗溴脱氧尿核苷(BrdU)或OX42和抗BrdU双重免疫荧光染色显示，BrdU掺入的小胶质细胞主要存在于初始和高峰阶段，提示小胶质细胞通过细胞分裂增殖形成胶质细胞，而星形细胞胶质细胞增生可能是星形胶质细胞迁移和/或GFAP分子表达上调的结果。综合以前的体外研究结果，小胶质细胞，而不是星形胶质细胞，刺激了脑源性T细胞的增殖，这些体内发现表明，小胶质细胞增强，而星形胶质细胞抑制，在中枢神经系统的炎症过程。
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 antibromodeoxyuridine (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.