The plasminogen activator/plasmin system is essential for development of the joint inflammatory phase of collagen type II-induced arthritis.

• The plasminogen activator (PA) system has been proposed to have important roles in rheumatoid arthritis. Here we have used the autoimmune collagen type II (CII)-induced arthritis (CIA) model and mice deficient for urokinase-type PA (uPA) or plasminogen to investigate the role of the PA system for development of arthritis. Our data revealed that uPA-deficient mice have a lower severity and incidence of CIA than wild-type mice. Furthermore, although >80% of wild-type control mice developed CIA, we found that none of the 50 plasminogen-deficient littermates that were tested developed CIA within a 40-day period. Antibody generation after CII immunization as well as the binding of labeled anti-CII antibodies to the surface of cartilage were similar in wild-type and plasminogen-deficient mice. No sign of inflammation was seen when plasminogen-deficient mice were injected with a mixture of monoclonal antibodies against CII. However, after daily injections of human plasminogen, these mice developed arthritis within 5 days. Our finding that infiltration of inflammatory cells into the synovial joints was impaired in plasminogen-deficient mice suggests that uPA and plasminogen are important mediators of joint inflammation. Active plasmin is therefore essential for the induction of pathological inflammatory joint destruction in CIA.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Nyckelord

Animals

Antibodies; Monoclonal/chemistry

Arthritis/*immunology/pathology

Arthritis; Experimental/*immunology/pathology

Collagen Type II/*metabolism

Enzyme-Linked Immunosorbent Assay

Epitopes

Immunohistochemistry

Inflammation/*metabolism

Joints/*immunology

Mice

Mice; Inbred C57BL

Plasmin/*metabolism

Plasminogen/*metabolism/*physiology

Plasminogen Activators/*metabolism

Time Factors

Urinary Plasminogen Activator/*physiology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)