Immune reactivity in a mouse model of familial ALS correlates with disease progression
Immune reactivity in a mouse model of familial ALS correlates with disease progression
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DOI：
10.1212/wnl.57.7.1282
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发表时间：
2001-10-09
期刊：
影响因子：
9.9
通讯作者：
Appel, SH
中科院分区：
文献类型：
--
作者：
Alexianu, ME;Kozovska, M;Appel, SH
目的：肌萎缩侧索硬化症运动神经元死亡的原因尚不完全清楚。本研究旨在确定非神经元免疫炎症因子在突变型超氧化物歧化酶-1 （SOD1）转基因小鼠运动神经元破坏中的潜在参与，并将其作为ALS模型。背景：ALS患者和运动神经元疾病实验动物模型脊髓中存在活化的小胶质细胞、IgG及其铁部分受体（Fc γ RI）和T淋巴细胞，强烈提示免疫炎症因子可能积极参与疾病过程。方法：观察不同年龄（40、80、120日龄）人突变型（G93A） SOD1转基因小鼠和人野生型SOD1转基因小鼠免疫炎性因子的表达。用CD11b、IgG、Fc γ RI、细胞间粘附分子-1 （ICAM-1）、CD3和胶质原纤维酸性蛋白抗体对固定、冷冻和自由漂浮的腰椎脊髓切片进行染色。结果：在40日龄SOD1突变小鼠中，最早观察到的变化是前腰脊髓ICAM-1表达上调。早在40天运动神经元和后期小胶质细胞上检测IgG和Fc γ RI的反应性。小胶质细胞的激活首先在80天的腹角出现，而反应性星形胶质细胞和T细胞在120天的SOD1突变小鼠中最为突出。结论：SOD1基因突变小鼠在症状前早期促炎因子的上调以及随着疾病进展免疫激活的扩大提示免疫炎症机制可能促进疾病进展。
Objective: The cause of motor neuron death in ALS is incompletely understood. This study aims to define the potential involvement of nonneuronal immune-inflammatory factors in the destruction of motor neurons in mutant superoxide dismutase-1 (SOD1) transgenic mice as a model of ALS. Background: The presence of activated microglia, IgG and its receptor for Fe portion (Fc gamma RI), and T lymphocytes in the spinal cord of both patients with ALS and experimental animal models of motor neuron disease strongly suggests that immune-inflammatory factors may be actively involved in the disease process. Methods: The expression of immune-inflammatory factors was followed in both human mutant (G93A) SOD1 transgenic mice and human wild-type SOD1 transgenic mice, at different ages (40, 80, and 120 days). Fixed, frozen, free-floating sections of the lumbar spinal cord were stained with antibodies against CD11b, IgG, Fc gamma RI, intercellular adhesion molecule-1 (ICAM-1), CD3, and glial fibrillary acidic protein. Results: The earliest change observed was the upregulation of ICAM-1 in the ventral lumbar spinal cord of 40-day-old mutant SOD1 mice. IgG and Fc gamma RI reactivities were detected on motor neurons as early as 40 days and on microglial cells at later stages. Microglial activation was first evident in the ventral horn at 80 days, whereas reactive astrocytes and T cells became most prominent in 120-day-old mutant SOD1 mice. Conclusion: The upregulation of proinflammatory factors during early presymptomatic stages as well as the expansion of immune activation as disease progresses in mutant SOD1 transgenic mice suggest that immune-inflammatory mechanisms could contribute to disease progression.