{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:16:49Z","timestamp":1787836609249,"version":"build-2784847793"},"reference-count":53,"publisher":"American Physiological Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2013,11,15]]},"abstract":"<jats:p>Intrapleural processing of prourokinase (scuPA) in tetracycline (TCN)-induced pleural injury in rabbits was evaluated to better understand the mechanisms governing successful scuPA-based intrapleural fibrinolytic therapy (IPFT), capable of clearing pleural adhesions in this model. Pleural fluid (PF) was withdrawn 0\u201380 min and 24 h after IPFT with scuPA (0\u20130.5 mg\/kg), and activities of free urokinase (uPA), plasminogen activator inhibitor-1 (PAI-1), and uPA complexed with \u03b1-macroglobulin (\u03b1M) were assessed. Similar analyses were performed using PFs from patients with empyema, parapneumonic, and malignant pleural effusions. The peak of uPA activity (5\u201340 min) reciprocally correlated with the dose of intrapleural scuPA. Endogenous active PAI-1 (10\u201320 nM) decreased the rate of intrapleural scuPA activation. The slow step of intrapleural inactivation of free uPA ( t<jats:sub>1\/2<\/jats:sub><jats:sup>\u03b2<\/jats:sup>= 40 \u00b1 10 min) was dose independent and 6.7-fold slower than in blood. Up to 260 \u00b1 70 nM of \u03b1M\/uPA formed in vivo [second order association rate ( k<jats:sub>ass<\/jats:sub>) = 580 \u00b1 60 M<jats:sup>\u22121<\/jats:sup>\u00b7s<jats:sup>\u22121<\/jats:sup>]. \u03b1M\/uPA and products of its degradation contributed to durable intrapleural plasminogen activation up to 24 h after IPFT. Active PAI-1, active \u03b1<jats:sub>2<\/jats:sub>M, and \u03b1<jats:sub>2<\/jats:sub>M\/uPA found in empyema, pneumonia, and malignant PFs demonstrate the capacity to support similar mechanisms in humans. Intrapleural scuPA processing differs from that in the bloodstream and includes 1) dose-dependent control of scuPA activation by endogenous active PAI-1; 2) two-step inactivation of free uPA with simultaneous formation of \u03b1M\/uPA; and 3) slow intrapleural degradation of \u03b1M\/uPA releasing active free uPA. This mechanism offers potential clinically relevant advantages that may enhance the bioavailability of intrapleural scuPA and may mitigate the risk of bleeding complications.<\/jats:p>","DOI":"10.1152\/ajplung.00102.2013","type":"journal-article","created":{"date-parts":[[2013,8,31]],"date-time":"2013-08-31T03:56:13Z","timestamp":1377921373000},"page":"L682-L692","source":"Crossref","is-referenced-by-count":19,"title":["Active \u03b1-macroglobulin is a reservoir for urokinase after fibrinolytic therapy in rabbits with tetracycline-induced pleural injury and in human pleural fluids"],"prefix":"10.1152","volume":"305","author":[{"given":"Andrey A.","family":"Komissarov","sequence":"first","affiliation":[{"name":"The Texas Lung Injury Institute, The University of Texas Health Science Center at Tyler, Tyler, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina","family":"Florova","sequence":"additional","affiliation":[{"name":"The Texas Lung Injury Institute, The 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