title: Essential role for the C5a receptor in regulating the effector phase of synovial infiltration and joint destruction in experimental arthritis.
abstract: A characteristic feature of rheumatoid arthritis is the abundance of inflammatory cells in the diseased joint. Two major components of this infiltrate are neutrophils in the synovial fluid and macrophages in the synovial tissue. These cells produce cytokines including tumor necrosis factor alpha and other proinflammatory mediators that likely drive the disease through its effector phases. To investigate what mechanisms underlie the recruitment of these cells into the synovial fluid and tissue, we performed expression analyses of chemoattractant receptors in a related family that includes the anaphylatoxin receptors and the formyl-MetLeuPhe receptor. We then examined the effect of targeted disruption of two abundantly expressed chemoattractant receptors, the receptors for C3a and C5a, on arthritogenesis in a mouse model of disease. We report that genetic ablation of C5a receptor expression completely protects mice from arthritis.
authors.affiliation: Millennium Pharmaceuticals, Inc., 75 Sidney Street, Cambridge, MA 02139, USA. egrant@mpi.com
authors.forename: Ethan P
authors.initials: EP
authors.lastname: Grant
authors.forename: Dominic
authors.initials: D
authors.lastname: Picarella
authors.forename: Timothy
authors.initials: T
authors.lastname: Burwell
authors.forename: Tracy
authors.initials: T
authors.lastname: Delaney
authors.forename: Alisa
authors.initials: A
authors.lastname: Croci
authors.forename: Nicole
authors.initials: N
authors.lastname: Avitahl
authors.forename: Alison A
authors.initials: AA
authors.lastname: Humbles
authors.forename: Jose-Carlos
authors.initials: JC
authors.lastname: Gutierrez-Ramos
authors.forename: Michael
authors.initials: M
authors.lastname: Briskin
authors.forename: Craig
authors.initials: C
authors.lastname: Gerard
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Coyle
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D001168:Arthritis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003094:Collagen / Q000276:immunology; D003167:Complement Activation; D003182:Complement C5 / Q000502:physiology; D019040:E-Selectin / Q000096:biosynthesis; D015870:Gene Expression; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007596:Joints / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D017463:Receptors, Complement 3b / Q000032:analysis / Q000502:physiology; D013583:Synovial Membrane / Q000473:pathology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D015703:Antigens, CD; D003182:Complement C5; D019040:E-Selectin; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D003094:Collagen