An important role for the chemokine macrophage inflammatory protein-1 alpha in the pathogenesis of the T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis.
An important role for the chemokine macrophage inflammatory protein-1 alpha in the pathogenesis of the T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis.
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DOI：
10.4049/jimmunol.155.10.5003
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发表时间：
1995-11
影响因子：
4.4
通讯作者：
W. Karpus;N. Lukacs;B. Mcrae;R. Strieter;S. Kunkel;Stephen D. Miller
中科院分区：
文献类型：
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作者：
W. Karpus;N. Lukacs;B. Mcrae;R. Strieter;S. Kunkel;Stephen D. Miller
实验性自身免疫性脑脊髓炎(EAE)是一种由CD4+T细胞介导的中枢神经系统(CNS)炎症性脱髓鞘疾病，是人类多发性硬化症的模型。在EAE发病机制中的一个关键事件是Ag特异性T淋巴细胞和非Ag特异性单个核细胞进入中枢神经系统。在本报告中，我们探讨了两种C-C趋化因子(巨噬细胞炎性蛋白-1α(MIP-1α)和单核细胞趋化蛋白-1)和一种C-x-C趋化因子(MIP-2)在EAE发病中的作用。中枢神经系统中MIP-1α的产生与严重临床疾病的发生有关，但与啮齿动物IL-8或单核细胞趋化蛋白-1的同源物MIP-2的产生无关。使用抗MIP-1α，但不使用抗单核细胞趋化蛋白-1，可以防止急性和复发麻痹性疾病的发展，以及由神经抗原肽激活的T细胞转移引发的单个核细胞向中枢神经系统的渗透。AB疗法也可用于改善正在进行的临床疾病的严重程度。通过细胞因子分泌、表面标志物的表达和过继转移EAE的能力来衡量，抗MIP-1α不影响脑源性T细胞的激活。这些结果表明，MIP-1α在T细胞介导的自身免疫性疾病(EAE)中对单核炎性细胞的趋化作用具有重要作用。
Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated, inflammatory demyelinating disease of the central nervous system (CNS) that serves as a model for the human demyelinating disease, multiple sclerosis. A critical event in the pathogenesis of EAE is the entry of both Ag-specific T lymphocytes and Ag-nonspecific mononuclear cells into the CNS. In the present report we investigated the role of two C-C chemokines (macrophage inflammatory protein-1 alpha (MIP-1 alpha) and monocyte chemotactic protein-1) and a C-x-C chemokine (MIP-2) in the pathogenesis of EAE. Production in the CNS of MIP-1 alpha, but not that of MIP-2, a rodent homologue of IL-8, or monocyte chemotactic protein-1, correlated with development of severe clinical disease. Administration of anti-MIP-1 alpha, but not that of anti-monocyte chemotactic protein-1, prevented the development of both acute and relapsing paralytic disease as well as infiltration of mononuclear cells into the CNS initiated by the transfer of neuroantigen peptide-activated T cells. Ab therapy could also be used to ameliorate the severity of ongoing clinical disease. Anti-MIP-1 alpha did not affect the activation of encepahlitogenic T cells as measured by cytokine secretion, surface marker expression, and ability to adoptively transfer EAE. These results demonstrate that MIP-1 alpha plays an important role in directing the chemoattraction of mononuclear inflammatory cells in the T cell-mediated autoimmune disease, EAE.