Acute and relapsing experimental autoimmune encephalomyelitis are regulated by differential expression of the CC chemokines macrophage inflammatory protein-1α and monocyte chemotactic protein-1
Acute and relapsing experimental autoimmune encephalomyelitis are regulated by differential expression of the CC chemokines macrophage inflammatory protein-1α and monocyte chemotactic protein-1
复制标题
DOI：
10.1016/s0165-5728(98)00187-8
复制
发表时间：
1998-12-01
影响因子：
3.3
通讯作者：
Karpus, WJ
中科院分区：
文献类型：
--
作者：
Kennedy, KJ;Strieter, RM;Karpus, WJ
实验性自身免疫性脑脊髓炎（EAE）是一种T淋巴细胞介导的中枢神经系统（CNS）疾病，其特征是单核细胞浸润和脱髓鞘导致瘫痪。我们在整个疾病过程中检测了CNS中CC趋化因子的表达，发现巨噬细胞炎性蛋白（MIP）-1 α的产生与急性疾病严重程度的增加相关，并且在慢性复发性疾病中保持升高。相比之下，单核细胞趋化蛋白（MCP）-1表达的实质性水平没有观察到，直到在急性疾病的晚期，并继续在疾病的复发阶段是明显的。MCP-1表达与临床复发严重程度增加相关。在整个病程中，CNS中RANTES水平较低，但与急性或复发性疾病几乎没有相关性。尽管在整个疾病过程中观察到RANTES表达，但抗RANTES治疗对临床疾病进展没有影响。在复发性EAE期间，抗MCP-1而非抗MIP-1 α治疗降低了复发性疾病的临床严重性。此外，抗MCP-1治疗减少了复发性EAE期间的CNS巨噬细胞积累。这些结果表明，MIP-1 α控制急性EAE期间的单核细胞积聚，而MCP-1控制复发EAE期间的单核细胞浸润。(C)1998 Elsevier Science B. V.保留所有权利。
Experimental autoimmune encephalomyelitis (EAE) is a T lymphocyte-mediated disease of the central nervous system (CNS), characterized by mononuclear cell infiltration and demyelination resulting in paralysis. We examined CC chemokine expression in the CNS throughout the entire course of the disease and found that the production of macrophage inflammatory protein (MIP)-1 alpha correlated with increasing acute disease severity and remained elevated throughout chronic, relapsing disease. In contrast, a substantial level of monocyte chemotactic protein (MCP)-1 expression was not observed until late in acute disease and continued to be evident in the relapsing phase of the disease. MCP-1 expression correlated with increasing severity of clinical relapses. Lower levels of RANTES in the CNS were noted throughout the disease course, but showed little correlation with either acute or relapsing disease. Although RANTES expression was observed during the entire course of disease, anti-RANTES treatment had no effect on clinical disease progression. Anti-MCP-l, but not anti-MIP-1 alpha, treatment during relapsing EAE decreased clinical severity of relapsing disease. Furthermore, anti-MCP-l treatment reduced CNS macrophage accumulation during relapsing EAE. These results suggest that MIP-1 alpha controls mononuclear cell accumulation during acute EAE, while MCP-1 controls mononuclear cell infiltration during relapsing EAE. (C) 1998 Elsevier Science B.V. All rights reserved.