Effects of complement C5 on apoptosis in experimental autoimmune encephalomyelitis.
Complement activation is involved in the initiation of Ab-mediated inflammatory demyelination in experimental autoimmune encephalomyelitis (EAE). At a sublytic dose, the C5b-9 membrane attack complex protects oligodendrocytes (OLG) from apoptosis. Using C5-deficient (C5-d) mice, we previously showed a dual role for C5: enhancement of inflammatory demyelination in acute EAE, and promotion of remyelination during recovery. In this study, we investigated the role of C5 in apoptosis in myelin-induced EAE. In acute EAE, C5-d and C5-sufficient (C5-s) mice had similar numbers of total apoptotic cells, whereas C5-s had significantly fewer than C5-d during recovery. In addition, although both groups of mice displayed TUNEL(+) OLG, there were significantly fewer in C5-s than in C5-d during both acute EAE and recovery. Gene array and immunostaining of apoptosis-related genes showed that Fas ligand expression was higher in C5-s. In C5-s mice, Fas(+) cells were also higher than in C5-d mice in acute EAE; however, these cells were significantly reduced during recovery. Together, these findings are consistent with the role of C5, possibly by forming the membrane attack complex, in limiting OLG apoptosis in EAE, thus promoting remyelination during recovery.
Niculescu
Teodora
T
Department of Pathology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.
Weerth
Susanna
S
Niculescu
Florin
F
Cudrici
Cornelia
C
Rus
Violeta
V
Raine
Cedric S
CS
Shin
Moon L
ML
Rus
Horea
H
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D002452:Cell Count; D003167:Complement Activation / Q000235:genetics; D003182:Complement C5 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D053222:Fas Ligand Protein; D005260:Female; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000276:immunology / Q000473:pathology; D009836:Oligodendroglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019014:fas Receptor / Q000096:biosynthesis / Q000378:metabolism
D003182:Complement C5; D015938:Complement Membrane Attack Complex; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor