ZYMOGRAPHIC EVALUATION OF PLASMINOGEN ACTIVATORS AND PLASMINOGEN ACTIVATOR INHIBITORS

摘要

Normal wound healing is controlled by fibrin deposition and its subsequent removal via a highly regulated complex of proteases and protease inhibitors, i.e., the plasminogen activator/plasminogen activator inhibitor (PA/PAI) system (A7, G3, H8, II, L4, L7, S2, W3, W7, X2). Fibrin degradation is mediated by the activity of plasmin generated from its zymogen, plasminogen, by tissue type plasminogen activator (tPA), or urokinase type plasminogen activator (uPA) (F7, H6, R2, VI). PA activity is balanced through its specific interaction with fibrin as well as its endogenous inhibitors, plasminogen activator inhibi-tor-1 (PAI-1), and PAI-2 (A3, B3, B4, K5, K7, Wl). Although the PA/PAI system serves the primary role in mediating fibrinolysis, other proteases (elas-tase, cathepsin) and serpin-type protease inhibitors (ai-antiplasmin, Cl inhibitor) appear to be involved in this process, albeit less specifically (A6, B4, VI). In addition to its ability to bind PAs, fibrin acts as a reserve of other enzymes that participate in its deposition (thrombin), stabilization (transglutaminase), and resolution (plasminogen) (F7, H6, R2, VI). Fibrin also provides a structural framework for wound stabilization as well as a functional matrix for cell migration and subsequent collagen elaboration (K8, SI, V2). The action of its associated PA/PAI system result in the production of fibrin-derived peptides that can further regulate wound healing, i.e., neutrophil-derived chemotaxis, elaboration of cytokines from inflammatory cells, and adhesion and migration of fibroblasts, via remodeling of the extracellular matrix (B7, B8, F5, Gil, HI, L5, Sll).