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The blood circulating zymogens of these proteases enter damaged tissue as a consequence of vascular leak or rupture to become activated and contribute to extravascular coagulation or fibrinolysis. The coagulants, factor Xa (FXa), factor VIIa (FVIIa), tissue factor, and thrombin, also evoke cell\u2010mediated actions on structural cells (e.g., fibroblasts and smooth muscle cells) or inflammatory cells (e.g., macrophages) via the proteolytic activation of protease\u2010activated receptors (PARs). Plasmin, the principle enzymatic mediator of fibrinolysis, also forms toll\u2010like receptor\u20104 (TLR\u20104) activating fibrin degradation products (FDPs) and can release latent\u2010matrix bound growth factors such as transforming growth factor\u2010<jats:italic>\u03b2<\/jats:italic> (TGF\u2010<jats:italic>\u03b2<\/jats:italic>). Furthermore, the proteases that convert plasminogen into plasmin (e.g., urokinase plasminogen activator) evoke plasmin\u2010independent proinflammatory actions involving coreceptor activation. Selectively targeting the receptor\u2010mediated actions of hemostatic proteases is a strategy that may be used to treat inflammatory disease without the bleeding complications of conventional anticoagulant therapies. The mechanisms by which proteases of the coagulant and fibrinolytic systems contribute to extravascular inflammation in disease will be considered in this review.<\/jats:p>","DOI":"10.1155\/2015\/437695","type":"journal-article","created":{"date-parts":[[2015,3,24]],"date-time":"2015-03-24T23:32:38Z","timestamp":1427239958000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":102,"title":["The Inflammatory Actions of Coagulant and Fibrinolytic Proteases in Disease"],"prefix":"10.1155","volume":"2015","author":[{"given":"Michael","family":"Schuliga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,3,24]]},"reference":[{"key":"e_1_2_17_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00016.2011"},{"key":"e_1_2_17_2_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1334486"},{"key":"e_1_2_17_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci200419569"},{"key":"e_1_2_17_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci60323"},{"key":"e_1_2_17_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/16.suppl_A.11"},{"key":"e_1_2_17_6_2","doi-asserted-by":"publisher","DOI":"10.2174\/138920111798281144"},{"key":"e_1_2_17_7_2","first-page":"993","article-title":"Monoclonal antibodies for immunodetection of fibrin deposits on cancer cells","volume":"28","author":"Schardt F. 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