Pathak Monika, Kaira Bubacarr Gibril, Slater Alexandre, Emsley Jonas
Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom.
Front Med (Lausanne). 2018 Mar 21;5:66. doi: 10.3389/fmed.2018.00066. eCollection 2018.
The contact activation system (CAS) or contact pathway is central to the crosstalk between coagulation and inflammation and contributes to diverse disorders affecting the cardiovascular system. CAS initiation contributes to thrombosis but is not required for hemostasis and can trigger plasma coagulation the intrinsic pathway [through factor XI (FXI)] and inflammation bradykinin release. Activation of factor XII (FXII) is the principal starting point for the cascade of proteolytic cleavages involving FXI, prekallikrein (PK), and cofactor high molecular weight kininogen (HK) but the precise location and cell receptor interactions controlling these reactions remains unclear. FXII, PK, FXI, and HK utilize key protein domains to mediate binding interactions to cognate cell receptors and diverse ligands, which regulates protease activation. The assembly of contact factors has been demonstrated on the cell membranes of a variety of cell types and microorganisms. The cooperation between the contact factors and endothelial cells, platelets, and leukocytes contributes to pathways driving thrombosis yet the basis of these interactions and the relationship with activation of the contact factors remains undefined. This review focuses on cell receptor interactions of contact proteins and FXI to develop a cell-based model for the regulation of contact activation.
接触激活系统（CAS）或接触途径是凝血与炎症之间相互作用的核心，并且与影响心血管系统的多种疾病相关。CAS的启动会导致血栓形成，但并非止血所必需，并且可以触发血浆凝血（内源性途径[通过因子XI（FXI）]）和炎症（缓激肽释放）。因子XII（FXII）的激活是涉及FXI、前激肽释放酶（PK）和辅因子高分子量激肽原（HK）的蛋白水解裂解级联反应的主要起始点，但控制这些反应的精确位置和细胞受体相互作用仍不清楚。FXII、PK、FXI和HK利用关键蛋白结构域介导与同源细胞受体和多种配体的结合相互作用，从而调节蛋白酶激活。已经在多种细胞类型和微生物的细胞膜上证实了接触因子的组装。接触因子与内皮细胞、血小板和白细胞之间的协同作用促成了驱动血栓形成的途径，但这些相互作用的基础以及与接触因子激活的关系仍不明确。本综述重点关注接触蛋白和FXI的细胞受体相互作用，以建立一个基于细胞的接触激活调节模型。
