Factor XII (FXII) is a protease that is mainly produced in the liver and circulates in plasma as a single chain zymogen. Following contact with negatively charged surfaces, FXII is converted into the two-chain active form, FXIIa. FXIIa initiates the intrinsic blood coagulation pathway via activation of factor XI. Furthermore, it converts plasma prekallikrein to kallikrein (PK), which reciprocally activates FXII and liberates bradykinin from high molecular weight kininogen. In addition, FXIIa initiates fibrinolysis via PK-mediated urokinase activation and activates the classical complement pathway. Even though the main function of FXII seems to relate to the activation of the intrinsic coagulation pathway and the kallikrein-kinin system, a growing body of evidence suggests that FXII may also directly regulate cellular responses. In this regard, it has been found that FXII/FXIIa induces the expression of inflammatory mediators, promotes cell proliferation, and enhances the migration of neutrophils and lung fibroblasts. In addition, it has been reported that genetic ablation of FXII protects against neuroinflammation, reduces the formation of atherosclerotic lesions in Apoe^−/− mice, improves wound healing, and inhibits postnatal angiogenesis. Although the aforementioned effects can be partially explained by the downstream products of FXII activation, the ability of FXII/FXIIa to directly regulate cellular responses has recently emerged as an alternative hypothesis. These direct cellular reactions to FXII/FXIIa will be discussed in the review.

因子XII（FXII）是一种蛋白酶，主要在肝脏中产生，并作为单链酶原在血浆中循环。与带负电的表面接触后，FXII转换为两链活性形式FXIIa。FXIIa通过激活因子XI来启动内在的凝血途径。此外，它可以将血浆前激肽释放酶转化为激肽释放酶（PK），后者可以相互激活FXII，并从高分子量激肽原中释放缓激肽。此外，FXIIa通过以下途径启动纤维蛋白溶解PK介导的尿激酶激活并激活经典补体途径。尽管FXII的主要功能似乎与内在凝血途径和激肽释放酶激肽系统的激活有关，但越来越多的证据表明FXII也可能直接调节细胞反应。在这方面，已经发现FXII / FXIIa诱导炎性介质的表达，促进细胞增殖，并增强嗜中性粒细胞和肺成纤维细胞的迁移。此外，据报道，FXII的基因消融可防止神经炎症，减少Apoe中动脉粥样硬化病变的形成^-/-小鼠，改善伤口愈合，并抑制产后血管生成。尽管上述效果可以由FXII激活的下游产物部分解释，但是FXII / FXIIa直接调节细胞反应的能力最近已成为一种替代假设。这些对FXII / FXIIa的直接细胞反应将在本综述中进行讨论。