Myelin phagocytosis and remyelination of macrophage-enriched central nervous system aggregate cultures.
An increased level of myelin basic protein (MBP) degradation peptide 80-89, representative of myelin breakdown, is detected in myelinating foetal rat brain aggregate cultures supplemented with peritoneal macrophages at a time coinciding with the onset of myelination. During the period of myelination, the proportion of activated macrophages/microglia in the aggregates decreases, accompanied by a reduction in the content of MBP degradation products. During the recovery period following a demyelinating episode, the rate of MBP synthesis in antibody-treated standard aggregates was greater than in their medium controls. However, the rate of MBP accumulation was not as efficient in macrophage-enriched aggregates and was associated with persistently raised MBP peptide levels. Thus, as occurs in multiple sclerosis lesions, attempts at remyelination appear to be counterbalanced by macrophage-mediated demyelination, with the continued presence of degraded myelin rendering a local environment that is not fully conducive to remyelination.
Copelman
C A
CA
Department of Neurochemistry, Institute of Neurology, University College London, 1 Wakefield Street, London, WC1N 1PJ, United Kingdom.
Diemel
L T
LT
Gveric
D
D
Gregson
N A
NA
Cuzner
M L
ML
D000328:Adult; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D001921:Brain / Q000196:embryology* / Q000276:immunology / Q000378:metabolism; D002452:Cell Count; D048429:Cell Size / Q000276:immunology; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D053331:Ectodysplasins; D005333:Fetus; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D004676:Myelin Basic Protein / Q000276:immunology / Q000378:metabolism*; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018992:Myelin-Associated Glycoprotein / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D009416:Nerve Regeneration / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000906:Antibodies; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; C497886:BSG protein, human; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C079432:Bsg protein, rat; C506018:EDA protein, human; D053331:Ectodysplasins; C571326:MOG protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C571328:Mog protein, rat; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D051926:Basigin