title: Disruption of the C5a receptor gene fails to protect against experimental allergic encephalomyelitis.
abstract: Activation of the complement system generates the anaphylatoxic peptide C5a, which elicits a broad range of inflammatory activities. The biological activities of C5a are mediated through its binding to the widely expressed C5a receptor (C5aR), a G-protein-coupled seven transmembrane domain receptor. In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, the C5aR is expressed on monocytes/macrophages, reactive astrocytes and T cells infiltrating the central nervous system (CNS). To investigate the role of the C5aR in this T cell-driven autoimmune model, we induced EAE in C5aR-deficient mice (C5aR(-/-)) and wild-type mice using a myelin oligodendrocyte glycoprotein (MOG) peptide as the immunogen. We found that C5aR(-/-) mice were fully susceptible to MOG-induced EAE with no difference in disease onset or severity in C5aR(-/-) mice compared to control mice. Cellular infiltrates (macrophages and T cells) were similar in the spinal cords of both animal groups and splenic T cells from C5aR(-/-) mice and control mice responded identically to MOG in T cell proliferation assays. Ribonuclease protection assays demonstrated no significant differences in pro-inflammatory gene expression between receptor-deficient and sufficient mice. These results indicate that the C5aR is not an essential mediator in the induction and progression of EAE.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham 35294, USA.
authors.forename: Rachael
authors.initials: R
authors.lastname: Reiman
authors.forename: Craig
authors.initials: C
authors.lastname: Gerard
authors.forename: Iain L
authors.initials: IL
authors.lastname: Campbell
authors.forename: Scott R
authors.initials: SR
authors.lastname: Barnum
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D017252:CD3 Complex / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D003167:Complement Activation; D015936:Complement C5a / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D008213:Lymphocyte Activation; D016177:Macrophage-1 Antigen / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013116:Spinal Cord / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D015703:Antigens, CD; D017252:CD3 Complex; D018925:Chemokines; D016207:Cytokines; D016177:Macrophage-1 Antigen; D012333:RNA, Messenger; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D015936:Complement C5a