Oligodendroglia are protected from antibody-mediated complement injury by normal immunoglobulins ("IVIg").
High-dose intravenous immunoglobulin (IVIg) treatment has become a promising immune therapy that can modulate the immune system at several levels, including the complement cascade. In relation to inflammatory demyelinating disease, there is some clinical evidence for the suppression of disease activity by IVIg, while a role in promoting remyelination after experimental myelin damage has been described. Antibody and complement deposition have been implicated in the immune attack in some cases of multiple sclerosis (MS), and to investigate the mechanisms of action of IVIg, we studied the effect of IVIg using the model of complement-mediated cell injury on oligodendroglia in vitro. There was no effect on direct complement lysis of the oligodendroglial cell line CG4, but antibody-dependent complement damage was inhibited in a dose-dependent manner by IVIg. These results were confirmed with primary cultures of oligodendrocyte precursor cells (OPC) and oligodendrocytes. The addition of excess C1, C3, and C4 did not influence the inhibitory effect of IVIg, implying that binding of these complement components does not play a role, in contrast to other experimental models of complement damage. F(ab')2 immunoglobulin fragments were at least partially responsible for the effect. We conclude that IVIg may be protective in antibody-mediated complement injury of oligodendrocytes and their progenitors, and that this effect is likely to be mediated via antibody binding, rather than interference with complement activation. Inhibition of inflammatory mechanisms, as opposed to a direct effect on remyelinating cells, may underlie the role of IVIg in promoting myelin repair in experimental models.
Stangel
M
M
Neurology Unit, Addenbrooke's Hospital, University of Cambridge, UK. mstangel@zedat.fu-berlin.de
Compston
A
A
Scolding
N J
NJ
D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003167:Complement Activation / Q000187:drug effects* / Q000276:immunology; D003172:Complement C1 / Q000494:pharmacology; D003176:Complement C3 / Q000494:pharmacology; D003181:Complement C4 / Q000494:pharmacology; D003165:Complement System Proteins / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007150:Immunohistochemistry; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D003172:Complement C1; D003176:Complement C3; D003181:Complement C4; D007140:Immunoglobulin Fab Fragments; D016756:Immunoglobulins, Intravenous; D003165:Complement System Proteins