title: Mast cell chymase contributes to the antibody response and the severity of autoimmune arthritis.
abstract: 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.
authors.affiliation: Uppsala University, Department of Cell and Molecular Biology, Uppsala, Sweden.
authors.forename: Sofia E
authors.initials: SE
authors.lastname: Magnusson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Pejler
authors.forename: Sandra
authors.initials: S
authors.lastname: Kleinau
authors.forename: Magnus
authors.initials: M
authors.lastname: Abrink
mesh_terms: 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
chemical_list: D000906:Antibodies; D003094:Collagen; D012697:Serine Endopeptidases; C066932:mast cell protease 4