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          Institute: MPI für Neurobiologie     Collection: Neuroimmunology     Display Documents



ID: 15216.0, MPI für Neurobiologie / Neuroimmunology
MHC gene related effects on microglia and macrophages in experimental autoimmune encephalomyelitis determine the extent of axonal injury
Authors:Storch, M. K.; Weissert, R.; Stefferl, A.; Birnbacher, R.; Wallstrom, E.; Dahlman, I.; Ostensson, C. G.; Linington, C.; Olsson, T.; Lassmann, H.
Language:English
Date of Publication (YYYY-MM-DD):2002-07
Title of Journal:Brain Pathology
Journal Abbrev.:Brain Pathol.
Volume:12
Issue / Number:3
Start Page:287
End Page:299
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:Myelin-oligodendrocyte-glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in rats is a chronic inflammatory demyelinating disease of the central nervous system (CNS) strongly mimicking multiple sclerosis (MS). We determined the involvement of macrophages and microglia in the lesions of MOG-EAE in relation to different major histocompatibility complex (MHC, RT1 in rat) haplotypes. We used intra-RT1 recombinant rat strains with recombinations between the RT1(a) and RT1(u) haplotypes on the disease permissive LEW non-MHC genome. Activated microglia and macrophages were identified morphologically and by expression of ED1 and allograft inhibitory factor-1 (AIF-1), and differentiated by their morphological phenotype. White matter lesions contained more macrophages and less microglia compared to grey matter lesions. Similarly active lesions were mainly infiltrated by macrophages, while microglia were abundant in inactive demyelinated plaques. In addition, we found a highly significant genetic association between a macrophage or microglia dominated lesional phenotype, which was independent from location and activity of the lesions. This was not only the case in demyelinating plaques of chronic EAE, but also in purely inflammatory lesions of acute passive transfer EAE. Rat strains with an u-haplotype in both the Class II and the telomeric non-classical Class I region revealed inflammatory and demyelinating lesions, which were dominated by activated microglia. The a-haplotype in any of these regions was associated with macrophage dominated lesions. A comparison of lesions, exactly matched for stages of demyelinating activity in these different rat strains, showed that in spite of a similar extent of demyelination, axonal injury was significantly less in microglia compared to macrophage dominated lesions. Thus, our studies document a genetic influence of the MHC-region on the relative contribution of macrophages versus microglia in the pathogenesis of EAE.
External Publication Status:published
Document Type:Article
Affiliations:MPI für Neurobiologie/Neuroimmunology
External Affiliations:Univ Vienna, Brain Res Inst, Div Neuroimmunol, Spitalgasse 4,; A-1090 Vienna, Austria; Univ Vienna, Brain Res Inst, Div Neuroimmunol, A-1090 Vienna, Austria; Graz Univ, Dept Neurol, A-8010 Graz, Austria; Karolinska Hosp, Ctr Mol Med, Neuroimmunol Unit, S-10401 Stockholm, Sweden; Univ Tubingen, Dept Neurol, D-72074 Tubingen, Germany; Max Planck Inst Neurobiol, Dept Neuroimmunol, Martinsried, Germany; Univ Vienna, Dept Paediat, A-1010 Vienna, Austria; Karolinska Hosp, Dept Mol Med, Endocrine & Diabet Unit, S-10401 Stockholm, Sweden
Identifiers:ISI:000176772800002
ISSN:1015-6305
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