title: Complement activation by both classical and alternative pathways is critical for the effector phase of arthritis.
abstract: To analyze the role of the classical and alternative pathways of complement activation in the effector phase of arthritis, we have induced arthritis in C3- and factor B (FB)-deficient (C3(-/-) and FB(-/-)) DBA/1J mice using well-defined monoclonal IgG2b and IgG2a antibodies to type II collagen. In control DBA/1J mice, severe swelling of the joints, destruction of cartilage and erosion of bone developed very rapidly with a 100% incidence and a peak on days 7-10. Although 75% of C3(-/-) mice developed arthritis, the clinical severity was very mild and the onset was delayed. Severity of arthritis in FB(-/-) mice ranked intermediate in comparison with C3(-/-) and control mice with an incidence of 100%. Immunohistochemical analysis of the inflamed joints demonstrated substantial reduction in macrophage and neutrophilic leukocyte infiltration in both C3(-/-) and FB(-/-) mice, thereby confirming the clinical findings. We conclude that both the classical and the alternative pathways of complement activation are involved in the effector phase of arthritis.
authors.affiliation: Department of Medical Biochemistry, Göteborg University, Göteborg, Sweden.
authors.forename: Max Albert
authors.initials: MA
authors.lastname: Hietala
authors.forename: Kutty S
authors.initials: KS
authors.lastname: Nandakumar
authors.forename: Linda
authors.initials: L
authors.lastname: Persson
authors.forename: Susann
authors.initials: S
authors.lastname: Fahlén
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.forename: Marcela
authors.initials: M
authors.lastname: Pekna
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D003167:Complement Activation / Q000276:immunology*; D003176:Complement C3 / Q000172:deficiency; D011415:Complement Factor B / Q000172:deficiency; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007596:Joints / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology
chemical_list: D003176:Complement C3; D011415:Complement Factor B