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 | Sofia E Magnusson, Gunnar Pejler, Sandra Kleinau, Magnus Abrink |
Journal | FASEB journal : official publication of the Federation of American Societies for Experimental Biology
(FASEB J)
Vol. 23
Issue 3
Pg. 875-82
(Mar 2009)
ISSN: 1530-6860 [Electronic] United States |
PMID | 19010978
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antibodies
- Collagen
- Serine Endopeptidases
- mast cell protease 4
|
Topics |
- Animals
- Antibodies
(immunology)
- Arthritis, Experimental
(chemically induced, immunology)
- Arthritis, Rheumatoid
(immunology)
- Collagen
(toxicity)
- Female
- Joints
(cytology)
- Male
- Mast Cells
(physiology)
- Mice
- Mice, Inbred DBA
- Mice, Knockout
- Serine Endopeptidases
(metabolism)
- Time Factors
|