| Summary: | Abstract Factor XII (FXII) becomes a serine protease when blood is exposed to artificial medical surfaces or when pathologic surfaces arise in disease states leading to its autoactivation. Initiation of the blood coagulation cascade was the first recognized activity of FXIIa. Blocking FXIIa activity formed on artificial medical surfaces should reduce induced blood coagulation leading to thrombosis. In contrast to FXII enzymatic activities, less is known about zymogen FXII functions. Studies show that zymogen FXII has biologic activity in various cells in vivo. In endothelium, FXII stimulates cell growth and proliferation and, in vivo, neoangiogenesis after injury. In fibroblasts, transforming growth factor‐β increases FXII expression, which in turn stimulates fibroblast proliferation, contributing to tissue fibrosis. In neutrophils, FXII stimulates Akt2 to initiate neutrophil adhesion, migration, and chemotaxis, priming events leading to NETosis. Factor FXII deficiency leads to decreased neutrophil recruitment and improved wound healing. In dendritic cells, FXII contributes to neuroinflammation, and its deficiency or pharmacologic inhibition renders mice less susceptible to autoimmune encephalomyelitis. These combined studies indicate that FXII also contributes to multiple components of the inflammatory response. In sum, targeting FXII's biologic activities may provide novel approaches to reduce thrombosis and the inflammatory response in various disease states.
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