Thrombin in the Crossroad Hemostasis and Inflammation

Hemostasis and immune responses are evolutionarily and functionally related systems on the coordinated work of which vital processes-protection from pathogens and blood loss, depend. Thrombin is the central enzyme of the coagulation system, which has pronounced pro-inflammatory activity and plays an important role in the pathogenesis of a wide range of infectious and non-infectious diseases. Many humoral immune factors regulating inflammation (IL-1 alpha, C3 and C5 complement components) and cell migration to the lesion site (osteopontin, chemerin) are thrombin targets and become activated by proteolytic cleavage. The main thrombin receptors-protease-activating receptors (PARs), are expressed on immune cells and are considered as non-classical pattern-recognition receptors (PRRs). The effect of thrombin on innate immune cells may not be related to its enzymatic effects. Thrombin action on adaptive immunity is just beginning to be studied. Recent studies show that thrombin can serves as an alarmin, stimulate the maturation of dendritic cells and adaptive immune responses. The production of this factor also affects Th cell polarization, which determines immune response strategy. The study of the immune functions of the components of the coagulation system reveals new pathogenetic mechanisms of the development of sterile inflammation and expands existing possibilities of allergic, autoimmune and neuroinflammatory disease therapy.