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. © 2004 Wiley-VCH Verlag GmbH & Co. KGaA.