Abstract
Pleural empyema is characterized by excessive fibrin deposition and impaired fibrinolysis, largely driven by elevated plasminogen activator inhibitor-1 (PAI-1), which suppresses tissue plasminogen activator (tPA) activity. Current fibrinolytic therapies show variable efficacy and are often limited by PAI-1 inhibition. This study aimed to protect fibrinolytic activity from PAI-1 inhibition of tPA using monoclonal antibodies (mAbs) targeting PAI-1. A fluorescence-based FITC–fibrin 96-well assay was optimized to quantitatively monitor fibrin degradation. Using this platform, the effects of two mAbs, MA-55F4C12 and MA-56A7C10, were evaluated in vitro and ex vivo. Both antibodies protected tPA activity and enhanced plasmin generation by interfering with distinct steps of the PAI-1 inhibitory mechanism, including blocking PAI-1 binding to tPA, preventing stable PAI-1–tPA complex formation, and promoting PAI-1 inactivation. Combination treatment of mAbs demonstrated greater protection of fibrinolytic activity compared to individual antibodies, particularly under inhibitory conditions present in pleural fluid. These findings support a mechanism-based therapeutic strategy targeting PAI-1 to enhance fibrinolysis and improve treatment outcomes in pleural empyema.
Date of publication
Spring 5-2026
Document Type
Thesis (Local Only Access)
Language
english
Persistent identifier
http://hdl.handle.net/10950/5072
Degree
MS in Biotechnology
Recommended Citation
BASNET, MERINA, "TARGETING PLASMINOGEN ACTIVATOR INHIBITOR -1 TO PROTECT FIBRINOLYTIC ACTIVITY IN VITRO AND EX VIVO" (2026). Biotechnology Theses. Paper 41.
http://hdl.handle.net/10950/5072