Plasmin as a proinflammatory cell activator

The serine protease plasmin generated from its zymo-gen plasminogen is best known for its function as a key enzyme of the fibrinolytic cascade. However, beyond fibrinolysis, plasmin has a number of crucial functions in a variety of processes, including inflammation. Various cells can bind plasminogen and plasmin via plasmino-gen-binding sites exposing a C-terminal lysine. Plasmin, generated as a result of plasminogen activation at the cell surface, is protected from its physiological inhibi-tors. Apart from its ability to facilitate cell migration in tissues, plasmin is capable of triggering signaling, which depends on cellular binding via its lysine-binding sites and its proteolytic activity. Plasmin-induced sig-naling affects various functions of monocytes, macro-phages, DCs, and others, with the list of affected cells still growing. In vitro and in vivo studies have demon-strated the ability of plasmin to stimulate the production of cytokines, ROS, and other mediators, thereby con-tributing to inflammation. Plasmin-induced chemotaxis of monocytes and DCs indicates that it is also a potent chemoattractant for immune cells. Therefore, exces-sive activation of plasmin in chronic inflammatory or au-toimmune diseases might exacerbate the activation of inflammatory cells and the pathogenesis of the disease. This review focuses on the available evidence for physi-ological and pathophysiological roles the serine pro-tease plasmin in inflammatory processes. J. Leukoc. Biol. 92: 509–519; 2012