title: Blockade of the C5a receptor fails to protect against experimental autoimmune encephalomyelitis in rats.
abstract: Complement activation contributes to inflammation and tissue damage in human demyelinating diseases and in rodent models of demyelination. Inhibitors of complement activation ameliorate disease in the rat model antibody-dependent experimental autoimmune encephalomyelitis and rats unable to generate the membrane attack complex of complement develop inflammation without demyelination. The role of the highly active chemotactic and anaphylactic complement-derived peptide C5a in driving inflammation and pathology in rodent models of demyelination has been little explored. Here we have used a small molecule C5a receptor antagonist, AcF-[OPdChaWR], to examine the effects of C5a receptor blockade in rat models of brain inflammation and demyelination. C5a receptor antagonist therapy completely blocked neutrophil response to C5a in vivo but had no effect on clinical disease or resultant pathology in either inflammatory or demyelinating rat models. We conclude that C5a is not required for disease induction or perpetuation in these strongly complement-dependent disease models.
authors.affiliation: Complement Biology Group, Department of Medical Biochemistry and Immunology and Department of Pathology, UWCM, Cardiff, UK. morganbp@cardiff.ac.uk
authors.forename: B P
authors.initials: BP
authors.lastname: Morgan
authors.forename: M
authors.initials: M
authors.lastname: Griffiths
authors.forename: H
authors.initials: H
authors.lastname: Khanom
authors.forename: S M
authors.initials: SM
authors.lastname: Taylor
authors.forename: J W
authors.initials: JW
authors.lastname: Neal
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D003167:Complement Activation / Q000276:immunology*; D004679:Encephalomyelitis / Q000276:immunology* / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D020721:Nervous System Autoimmune Disease, Experimental / Q000276:immunology* / Q000473:pathology; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D044087:Receptor, Anaphylatoxin C5a / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology
chemical_list: D044087:Receptor, Anaphylatoxin C5a