Response of glia, mast cells and the blood brain barrier, in transgenic mice expressing interleukin-3 in astrocytes, an experimental model for CNS demyelination.
Response of glia, mast cells and the blood brain barrier, in transgenic mice expressing interleukin-3 in astrocytes, an experimental model for CNS demyelination.
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星形胶质细胞表达白细胞介素 3 的转基因小鼠中神经胶质细胞、肥大细胞和血脑屏障的反应，这是中枢神经系统脱髓鞘的实验模型。
DOI：
10.1111/j.1750-3639.1999.tb00220.x
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Campbell,IL
中科院分区：
文献类型：
--
作者：
Powell,HC;Garrett,RS;Brett,FM;Chiang,CS;Chen,E;Masliah,E;Campbell,IL
过表达细胞因子的转基因小鼠有助于分析这些免疫调节剂对中枢神经系统固有细胞的影响。本研究在最近描述的转基因模型（称为GFAP-IL 3）中检查脱髓鞘和渗透性变化的形态学方面。GFAP-IL 3小鼠在大约5个月时发展为进行性运动疾病。疾病发作后发现的病变显示小胶质细胞活化、星形胶质细胞增殖伴脂质吞噬作用以及巨噬细胞和肥大细胞向神经实质中的迁移。淋巴细胞直到疾病后期才出现。后来，小脑和脑干白色物质包含局灶性脱髓鞘病变，伴有强烈的巨噬细胞浸润和增生性星形细胞增多。除了严重浸润病变的脱髓鞘外，还观察到营养不良性轴突变化。野生型小鼠的丘脑和脑膜中存在的肥大细胞在GFAP-IL 3小鼠的这些部位大大增加。记录了血脑屏障（BBB）缺陷，静脉注射辣根过氧化物酶渗漏。肥大细胞浸润到CNS和它们在损伤部位的脱粒可能代表巨噬细胞介导的脱髓鞘的自发过程中的初始事件，其中神经胶质细胞和巨噬细胞都参与吞噬过程。
Transgenic mice overexpressing cytokines facilitate analysis of the effects of these immunomodulators on indigenous cells of the central nervous system. This study examines morphological aspects of demyelination and permeability changes, in a recently described transgenic model (termed GFAP‐IL3). GFAP‐IL3 mice develop progressive motor disease at approximately 5 months. Lesions identified after disease onset, showed activation of microglia, astroglial proliferation with phagocytosis of lipids, and immigration of macrophages and mast cells into neural parenchyma. Lymphocytes failed to appear until the later stages of the disease. Later, cerebellar and brain stem white matter contained focal demyelinating lesions with intense macrophage infiltration and a proliferative astrocytosis. Dystrophic axonal changes were noted, in addition to demyelination in heavily infiltrated lesions. Mast cells, variably present in the thalamus and meninges of wild type mice, were greatly increased at these sites in GFAP‐IL3 mice. Blood‐brain barrier (BBB) defects were documented with leakage of intravenously injected horseradish peroxidase. Mast cell infiltration into the CNS and their degranulation at the site of injury, may represent initial events in a spontaneous process of macrophage mediated demyelination in which glial cells and macrophages are both involved in the phagocytic process.