IntroductionUrokinase-type plasminogen activator (u-PA) has been implicated in fibrinolysis, cell migration, latent cytokine activation, cell activation, T cell activation, and tissue remodeling, all of which are involved in the development of rheumatoid arthritis. Previously, u-PA has been reported to play a protective role in monoarticular arthritis models involving mBSA as the antigen, but a deleterious role in the systemic polyarticular collagen-induced arthritis (CIA) model. The Aim of the current study is to determine how u-PA might be acting in systemic arthritis models.
Methods:
The CIA model and bone marrow chimeras were used to determine the cellular source of u-PA required for the arthritis development. Gene expression of inflammatory and destructive mediators was measured in joint tissue by quantitiative PCR and protein levels by ELISA. The requirement for u-PA in the type II collagen (CII)-mAb induced arthritis (CAIA) and K/BxN serum transfer arthritis models was determined using u-PA-/- mice. Neutrophilia was induced in the peritoneal cavity using either ovalbumin/anti-ovalbumin, or the complement component C5a.
Results:
u-PA from a bone marrow-derived cell was required for the full development of CIA. The disease in u-PA-/- mice reconstituted with bone marrrow from C57BL/6 mice was indistinguishable from that in C57BL/6 mice, in terms of clincal score, histologic features, and protein and gene expression of key mediators. u-PA-/- mice were resistant to both CAIA and K/BxN serum transfer arthritis development. u-PA-/- mice developed a reduced neutrophilia and chemokine production in the peritoneal cavity following OVA/anti-OVA injection; in contrast, the peritoneal neutrophilia in response to C5a was u-PA independent.
Conclusions:
u-PA is required for the full development of systemic arthritis models involving immune complex formation and deposition. The cellular source of u-PA required for CIA is bone marrow-derived and likely to be of myeloid origin. For immune complex-mediated peritonitis, and perhaps some other inflammatory responses, it is suggested that the u-PA involvement may be upstream of C5a signaling.

Further information:

Article source

Related posts:

1. c-Fms-mediated differentiation and priming of monocyte lineage cells plays a central role in autoimmune arthritis
2. Interleukin-17A upregulates receptor activator of NF-kappaB on osteoclast precursors
3. A rare case of primary systemic amyloidosis of the neck with massive cervical lymph node involvement: A case report and review of the literature
4. Role of PPAR-delta in the development of zymosan-induced multiple organ failure: an experiment mice study
5. Bone marrow cell transplants to benefit those with heart disease