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Complement activation by both classical and alternative pathways is critical for the effector phase of arthritis
Author(s) -
Hietala Max Albert,
Nandakumar Kutty S,
Persson Linda,
Fahlén Susann,
Holmdahl Rikard,
Pekna Marcela
Publication year - 2004
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200424895
Subject(s) - effector , arthritis , immunology , complement system , alternative complement pathway , monoclonal antibody , inflammation , biology , antibody , medicine
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.