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

Li, JinanUmeå universitet,Institutionen för medicinsk kemi och biofysik,Umeå University, Umeå, Sweden (author)

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.

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
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

Ny, AnneliiUmeå universitet,Institutionen för medicinsk kemi och biofysik,Umeå University, Umeå, Sweden; Flanders Interuniversity Institute for Biotechnology, KU Leuven, Leuven, Belgium (author)
Leonardsson, GöranUmeå universitet,Institutionen för medicinsk kemi och biofysik,Umeå University, Umeå, Sweden (author)
Nandakumar, Kutty Selva,1965-Lund University, Lund, Sweden(Swepub:hh)kutnam (author)
Holmdahl, RikardLund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Lund University, Lund, Sweden(Swepub:lu)infl-rho (author)
Ny, TorUmeå universitet,Institutionen för medicinsk kemi och biofysik,Umeå University, Umeå, Sweden(Swepub:umu)tony0001 (author)
Umeå universitetInstitutionen för medicinsk kemi och biofysik (creator_code:org_t)

In:American Journal of PathologyNew York : Elsevier166:3, s. 783-7920002-94401525-2191

By the author/editor: Li, Jinan; Ny, Annelii; Leonardsson, Gör ...; Nandakumar, Kutt ...; Holmdahl, Rikard; Ny, Tor

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

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