Journal
FASEB JOURNAL
Volume 23, Issue 3, Pages 875-882Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.08-120394
Keywords
protease and knockout mice; innate immune cell
Categories
Funding
- Swedish Research Council
- King Gustaf V 80-Year Foundation
- Swedish Rheumatism Association
- Goran Gustafsson Foundation
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Mast cells are implicated in rheumatoid arthritis, but the mechanism by which they contribute to disease progression is not clarified. Here we investigated whether mouse mast cell protease-4 (mMCP-4), a chymase present in the mast cell secretory granule, contributes to experimental arthritis. Two models of arthritis were investigated in mMCP-4(+/+) and mMCP-4(-/-) DBA/1 mice: collagen-induced arthritis ( CIA) was induced by immunization with collagen II (CII) in Freund's complete adjuvant, and a passive model of arthritis was induced by administration of anti-CII antibodies. The clinical scores were significantly reduced in the mMCP-4(-/-) animals as compared to mMCP-4(+/+) controls in both arthritis models. In CIA, the number of affected paws was lower in the CII-immunized mMCP-4(-/-) mice, with less cartilage destruction, pannus formation, and mononuclear cell and mast cell influx in the mMCP-4(-/-) joints. Interestingly, the lower clinical scores in the CII-immunized mMCP-4(-/-) mice coincided with lower serum levels of immunoglobulin G anti-CII antibodies. Our findings identify a pathogenic role of mMCP-4 in autoimmune arthritis.-Magnusson, S. E., Pejler, G., Kleinau, S., Abrink, M. Mast cell chymase contributes to the antibody response and the severity of autoimmune arthritis. FASEB J. 23, 875-882 (2009)
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