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., Åbrink, M. Mast cell chymase contributes to the antibody response and the severity of autoimmune arthritis.
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Mast cell chymase contributes to the antibody response and the severity of autoimmune arthritis
Magnusson, Sofia E.; Pejler, Gunnar; Kleinau, Sandra; Åbrink, Magnus
Follow The FASEB Journal
, Volume 23 (3): 875
Fed of American Socs for Experimental Biology – Mar 1, 2009
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