The FcRgamma chain is not essential for induction of experimental allergic encephalomyelitis (EAE) or anti-myelin antibody-mediated exacerbation of EAE.
Macrophages are considered essential mediators in multiple sclerosis (MS) pathogenesis, presumably through myelin phagocytosis and release of inflammatory mediators. Macrophages and microglia express activating Fcgamma receptors (FcgammaRI and FcgammaRIII), which depend on the FcRgamma chain for surface expression and signaling. In MS lesions, crosslinking of FcgammaR by immunoglobulins (IgG) directed against myelin may enhance myelin phagocytosis and inflammation. We studied the role of FcgammaR and anti-myelin antibodies in MOG35-55-induced experimental allergic encephalomyelitis (EAE) in C57BL/6 mice, a model of MS-like disease. Incidence and severity of EAE were similar in FcRy chain-/- (FcRgamma-/-) and wild-type (wt) mice, albeit with delayed onset in FcRgamma-/- mice. This demonstrates that the FcRy chain is not essential for induction of EAE, but that FcRgamma signaling may contribute to the preclinical phase. The role of FcgammaR in antibody-mediated demyelination was addressed by injection of anti-myelin antibodies (Z12 mAb) at onset of MOG35-55-induced EAE. Injection of Z12 mAb rapidly reduced survival time in both wt and FcRgamma-/- mice, demonstrating that antibody-mediated exacerbation of EAE is independent of the FcRgamma chain. Interestingly, Z12-induced exacerbation of inflammation and demyelination persisted longer in wt than FcRgamma-/- mice, suggesting that IgG-FcgammaR interactions may contribute to a sustained pathologic effect of anti-myelin antibodies in the CNS.
Breij
Esther C W
EC
Department of Molecular Cell Biology and Immunology, VU Medical Center, Amsterdam, The Netherlands. ecw.breij@vumc.nl
Heijnen
Priscilla
P
Vloet
Rianka
R
Saito
Takashi
T
van de Winkel
Jan G J
JG
Dijkstra
Christine D
CD
Amor
Sandra
S
Verbeek
Sjef
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D003711:Demyelinating Diseases / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D007249:Inflammation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000276:immunology*; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate
D000911:Antibodies, Monoclonal; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D021122:Protein Subunits; D017452:Receptors, IgG