Plasmin: A Modulator of Immune Function

Plasmin is the effector protease of the fibrinolytic system, well known for its involvement in fibrin degradation and clot removal. However, plasmin is also recognized as a potent modulator of immunological processes by directly interacting with various cell types including leukocytes (monocytes, macrophages, and dendritic cells) and cells of the vasculature (endothelial cells, smooth muscle cells) as well as soluble factors of the immune system and components of the extracellular matrix. In fact, the removal of misfolded proteins and maintenance of tissue homeostasis seem to be major physiological functions of plasmin. However, a large body of evidence also suggests that excessive plasmin generation frequently contributes to the pathophysiology of acute and chronic inflammatory processes. Hence, one question arising from the broadening effects of plasmin in physiology is whether antifibrinolytic drugs (i.e., tranexamic acid, epsilon aminocaproic acid, or aprotinin) that target plasmin either directly or indirectly and which are commonly used to prevent or treat bleeding might have unintended consequences on the immune response or on other nonfibrinolytic processes in vivo.