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.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

LANTBRUKSVETENSKAPER  -- Husdjursvetenskap (hsv//swe)

AGRICULTURAL SCIENCES  -- Animal and Dairy Sience (hsv//eng)

LANTBRUKSVETENSKAPER  -- Veterinärmedicin (hsv//swe)

AGRICULTURAL SCIENCES  -- Veterinary Science (hsv//eng)

Nyckelord

protease and knockout mice

innate immune cell

Biology

Biologi

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)