Expression of C5a in the brain does not exacerbate experimental autoimmune encephalomyelitis.
Complement is implicated in the pathology of neurodegenerative and inflammatory disease in the central nervous system (CNS). Although studies demonstrate that inhibition of complement activation attenuates disease development in the CNS, the specific complement components that contribute to the pathogenesis of CNS diseases remain unclear. To dissect the role of C5a in CNS disease, we developed a transgenic mouse that produces C5a exclusively in the brain using the astrocyte-specific, murine glial fibrillary acidic protein (GFAP) promoter. C5a/GFAP mice develop normally and do not demonstrate any signs of spontaneous inflammation or neurodegeneration with age. Using C5a/GFAP mice, we examined the outcome of the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). To our surprise the onset and severity of myelin oligodendrocyte glycoprotein-induced EAE was essentially identical between C5a/GFAP and control mice. These results demonstrate that C5a, despite it is pro-inflammatory functions, is not critical to the development and progression of EAE.
Reiman
Rachael
R
Department of Microbiology, University of Alabama at Birmingham, 845 19th St. S., Birmingham, AL 35294, USA.
Campos Torres
Antonio
A
Martin
Brian K
BK
Ting
Jenny P
JP
Campbell
Iain L
IL
Barnum
Scott R
SR
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D015936:Complement C5a / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D005455:Fluorescent Antibody Technique / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006023:Glycoproteins; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012720:Severity of Illness Index
D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D015936:Complement C5a