Figure 2.

Regulatory functions of FXII and FXIIa in sterile inflammation. Zymogen FXII functions as an autocrine messenger through uPAR to promote Akt2S⁴⁷⁴ phosphorylation. Propagation of FXII-mediated neutrophil activities includes adhesion, chemotaxis that leads to neutrophil trafficking at sites of inflammation and NET formation. Subsequent contact activation on the surface of preformed NETs leads to FXIIa generation and fibrin formation. In monocytes and macrophages, FXII and FXIIa upregulate the expression of pro-inflammatory mediators and promote cell polarization toward an M2 phenotype. In dendritic cells, FXII signals through uPAR to induce the differentiation of naive T-cells to TH17 cells. These immune cell responses contribute to impaired wound healing, propagation of venous thrombosis, tumor maintenance, and invasion as well as tissue damage during CNS autoimmunity. NETs, neutrophil extracellular traps; Mono, Monocytes; Macro, Macrophages; DC, Dendritic cells; TH17, T-helper cells.