Complement activation by both classical and alternative pathways is critical for the effector phase of arthritis

✍ Scribed by Max Albert Hietala; Kutty S Nandakumar; Linda Persson; Susann Fahlén; Rikard Holmdahl; Marcela Pekna

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 327 KB
• Volume: 34
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200424895

✦ Synopsis

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.