Remyelination of cytokine‐ or antibody‐demyelinated CNS aggregate cultures is inhibited by macrophage supplementation

GLIA - Tập 45 Số 3 - Trang 278-286 - 2004
Lara T. Diemel1, Guus Wolswijk2, Samuel J. Jackson1, M L Cuzner1
1Department of Neuroinflammation, Institute of Neurology, University College London, London, United Kingdom
2Netherlands Institute for Brain Research, Amsterdam, The Netherlands

Tóm tắt

AbstractRemyelination in CNS aggregate cultures is determined both by macrophage enrichment and the mode of demyelination. Despite the same degree of myelin loss, accumulation of MBP in anti‐MOG antibody‐demyelinated aggregates overtakes that of controls, while recovery is significantly delayed following IFN‐γ‐induced demyelination. In antibody‐treated cultures, remyelination was associated with a significant increase in culture supernatant levels of TGF‐β1, FGF‐2, and PDGF‐AA as well as an induction of TNF‐α immediately following removal of the demyelinating insult. The impaired recovery in IFN‐γ‐treated cultures, denoted by a significant reduction in TGF‐β1, was reversed by treatment with hrTGF‐β1. Macrophage supplementation of the cultures prior to the addition of either demyelinating agent induced a greater degree of myelin loss followed by incomplete remyelination in both cases. This failure to remyelinate was associated in both groups with a several‐fold elevation in TNF‐α and with modest increases in PDGF‐AA and FGF‐2 in the antibody‐treated cultures. In contrast, macrophage supplementation to mature cultures in the absence of any demyelinating treatment resulted in enhanced accumulation of MBP associated with a promyelinative growth factor and TNF‐α profile similar to that in aggregates enriched with macrophages at the outset of the culture period. Hence, effector elements of the adaptive immune response appear to override promyelinogenic in favor of proinflammatory macrophage factors in mature CNS aggregates, counteracting the potential for myelin repair. © 2003 Wiley‐Liss, Inc.

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Tài liệu tham khảo

10.1111/j.1460-9568.1996.tb01278.x

10.1016/S0002-9440(10)65622-2

10.1038/nn738

10.1002/(SICI)1098-1136(200006)30:4<342::AID-GLIA30>3.0.CO;2-8

10.1002/jnr.10026

10.1023/A:1022405516630

10.1002/jnr.10837

10.1083/jcb.129.2.443

10.1111/j.1365-2990.1987.tb00074.x

10.1002/neu.10158

10.1093/jnen/61.4.297

Guenard V, 1995, Transforming growth factor‐beta blocks myelination but not ensheathment of axons by Schwann cells in vitro, J Neurosci, 15, 419, 10.1523/JNEUROSCI.15-01-00419.1995

Hogg N, 1986, Macrophage antigens and the effect of a macrophage activating factor, interferon‐gamma, Ciba Found Symp, 118, 68

10.1007/978-1-4613-2473-7_7

Jensen MB, 2000, IFN gamma enhances microglial reactions to hippocampal axonal degeneration, J Neurosci, 20, 3612, 10.1523/JNEUROSCI.20-10-03612.2000

10.1002/(SICI)1097-4547(19990501)56:3<241::AID-JNR3>3.0.CO;2-H

10.1111/j.1365-2990.1993.tb00431.x

10.1016/0165-5728(84)90064-X

10.1002/jnr.490370512

10.1002/(SICI)1097-4547(19970215)47:4<384::AID-JNR3>3.0.CO;2-A

10.1016/S0021-9258(19)52451-6

10.1016/S0022-510X(02)00207-1

10.4049/jimmunol.163.11.6164

10.1007/BF02527713

10.1172/JCI112815

10.1038/nrn752

10.1093/brain/116.3.681

10.1073/pnas.79.8.2709

Selmaj K, 1991, Cytokine cytotoxicity against oligodendrocytes: apoptosis induced by lymphotoxin, J Immunol, 147, 1522, 10.4049/jimmunol.147.5.1522

10.1016/0012-1606(81)90477-2

Woodroofe MN, 1989, Fc receptor density, MHC antigen expression and superoxide production are increased in interferon‐gamma‐treated microglia isolated from adult rat brain, Immunology, 68, 421

10.1093/brain/awf031

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GLIA

Tập 45 Số 3

278-286

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