Mast cell chymase contributes to the antibody response and the severity of autoimmune arthritis.
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
Sofia E
SE
Uppsala University, Department of Cell and Molecular Biology, Uppsala, Sweden.
Pejler
Gunnar
G
Kleinau
Sandra
S
Abrink
Magnus
M
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D003094:Collagen / Q000633:toxicity; D005260:Female; D007596:Joints / Q000166:cytology; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D012697:Serine Endopeptidases / Q000378:metabolism*; D013997:Time Factors
D000906:Antibodies; D003094:Collagen; D012697:Serine Endopeptidases; C066932:mast cell protease 4