Complement activation by both classical and alternative pathways is critical for the effector phase of arthritis.
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.
Hietala
Max Albert
MA
Department of Medical Biochemistry, Göteborg University, Göteborg, Sweden.
Nandakumar
Kutty S
KS
Persson
Linda
L
Fahlén
Susann
S
Holmdahl
Rikard
R
Pekna
Marcela
M
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
D003176:Complement C3; D011415:Complement Factor B