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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.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>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 mAb-induced arthritis (CAIA) and K\/BxN serum transfer arthritis models was determined using u-PA<jats:sup>-\/-<\/jats:sup> mice. Neutrophilia was induced in the peritoneal cavity using either ovalbumin\/anti-ovalbumin or the complement component C5a.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>u-PA from a bone marrow-derived cell was required for the full development of CIA. The disease in u-PA<jats:sup>-\/-<\/jats:sup> 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<jats:sup>-\/-<\/jats:sup> mice were resistant to both CAIA and K\/BxN serum transfer arthritis development. u-PA<jats:sup>-\/-<\/jats:sup> mice developed a reduced neutrophilia and chemokine production in the peritoneal cavity following ovalbumin\/anti-ovalbumin injection; in contrast, the peritoneal neutrophilia in response to C5a was u-PA independent.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>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.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar2946","type":"journal-article","created":{"date-parts":[[2010,3,3]],"date-time":"2010-03-03T07:14:36Z","timestamp":1267600476000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Urokinase-type plasminogen activator and arthritis progression: role in systemic disease with immune complex involvement"],"prefix":"10.1186","volume":"12","author":[{"given":"Andrew D","family":"Cook","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine M","family":"De Nardo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma L","family":"Braine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda L","family":"Turner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ross","family":"Vlahos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerrie J","family":"Way","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S Kaye","family":"Beckman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason C","family":"Lenzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2010,3,2]]},"reference":[{"key":"2781_CR1","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1007\/PL00000615","volume":"56","author":"JP Irigoyen","year":"1999","unstructured":"Irigoyen JP, Munoz-Canoves P, Montero L, Koziczak M, Nagamine Y: The plasminogen activator system: biology and regulation. 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