Upregulation of monocyte chemotactic protein-1 and CC chemokine receptor 2 in the central nervous system is closely associated with relapse of autoimmune encephalomyelitis in Lewis rats.
Experimental autoimmune encephalomyelitis (EAE) is a disease model of multiple sclerosis (MS) that is characterized by remittance and relapse of the disease and autoimmune and demyelinating lesions in the central nervous system (CNS). To better understand the mechanism of disease relapse, we induced acute and chronic relapsing (CR)-EAE in Lewis rats and examined the differences between the two groups. An immunohistochemical study revealed that significantly higher numbers of macrophages infiltrated the spinal cord during the first and second attacks of CR-EAE than at the peak of acute EAE, whereas the number of infiltrating T cells was essentially the same in acute and CR-EAE. In accordance with this finding, monocyte chemoattractant protein-1 (MCP-1) mRNA, but not MIP-1alpha and RANTES mRNA, increased significantly in CR-EAE lesions rather than in acute EAE lesions. More importantly, the level of MCP-1 during the remission of CR-EAE was significantly higher than during the recovery phase of acute EAE, suggesting that this high level of MCP-1 in CR-EAE is associated with relapse of the disease. CC chemokine receptor 2 (CCR2), the main receptor for MCP-1, was expressed on astrocytes, macrophages and T cells and the number of positive cells was higher in CR-EAE than in acute EAE. Collectively, these findings suggest that high expression of MCP-1 and its receptor, CCR2, in the CNS play important roles in relapse of EAE.
Jee
Youngheun
Y
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Musashidai 2-6 Fuchu, Tokyo 183-8526, Japan.
Yoon
Won Kee
WK
Okura
Yoshio
Y
Tanuma
Naoyuki
N
Matsumoto
Yoh
Y
D000208:Acute Disease; D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics*; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D053331:Ectodysplasins; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D004727:Endothelium / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*
C515336:Ccr2 protein, rat; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D053331:Ectodysplasins; D008565:Membrane Proteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054390:Receptors, CCR2; D019707:Receptors, Chemokine