Granulocyte macrophage colony-stimulating factor: A new putative therapeutic target in multiple sclerosis

被引:329
作者
McQualter, JL
Darwiche, R
Ewing, C
Onuki, M
Kay, TW
Hamilton, JA
Reid, HH
Bernard, CCA [1 ]
机构
[1] La Trobe Univ, Dept Biochem, Neuroimmunol Lab, Bundoora, Vic 3086, Australia
[2] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Autoimmun & Transplantat Div, Melbourne, Vic 3050, Australia
[3] Univ Melbourne, Royal Melbourne Hosp, Dept Med, Arthrit & Inflammat Res Ctr, Melbourne, Vic 3050, Australia
关键词
multiple sclerosis; experimental autoimmune encephalomyelitis; GM-CSF; myelin oligodendrocyte glycoprotein; immune therapy;
D O I
10.1084/jem.194.7.873
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Experimental autoimmune encephalomyelitis (EA-E), a model for multiple sclerosis, can be induced by immunization with a number of myelin antigens. In particular, myelin oligodendrocyte glycoprotein, a central nervous system (CNS)-specific antigen expressed on the myelin surface, is able to induce a paralytic MS-like disease with extensive CNS inflammation and demyelination in several strains of animals. Although not well understood, the egress of immune cells into the CNS in EAE is governed by a complex interplay between pro and antiinflammatory cytokines and chemokines. The hematopoietic growth factor, granulocyte macrophage Colony-stimulating factor (GM-CSF). is considered to play a central role in maintaining chronic inflammation. The present study was designed to investigate the previously unexplored role of GM-CSF in autoimmune-mediated demyelination. GM-CSF-/- mice are resistant to EAE, display decreased antigen-specific proliferation of splenocytes, and fail to sustain immune cell infiltrates in the CNS, thus revealing key activities for GM-CSF in the development of inflammatory demyelinating lesions and control of migration and/or proliferation of leukocytes within the CNS. These results hold implications for the pathogenesis of inflammatory and demyelinating diseases and may provide the basis for more effective therapies for inflammatory diseases, and more specifically for multiple sclerosis.
引用
收藏
页码:873 / 881
页数:9
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