Heurich Meike, McCluskey Geneviève
School of Pharmacy and Pharmaceutical Sciences, College of Biomedical and Life Sciences, Cardiff University, United Kingdom.
Université Paris-Saclay, INSERM, Hémostase, Inflammation, Thrombose HITH U1176, 94276 Le Kremlin-Bicêtre, France.
Immunobiology. 2023 Nov;228(6):152707. doi: 10.1016/j.imbio.2023.152707. Epub 2023 Jul 12.
The immune complement and the coagulation systems are blood-based proteolytic cascades that are activated by pathway-specific triggers, based on protein-protein interactions and enzymatic cleavage reactions. Activation of these systems is finely balanced and controlled through specific regulatory mechanisms. The complement and coagulation systems are generally viewed as distinct, but have common evolutionary origins, and several interactions between these homologous systems have been reported. This complement and coagulation crosstalk can affect activation, amplification and regulatory functions in both systems. In this review, we summarize the literature on coagulation factors contributing to complement alternative pathway activation and regulation and highlight molecular interactions of the complement alternative pathway regulator factor H with several coagulation factors. We propose a mechanism where factor H interactions with coagulation factors may contribute to both complement and coagulation activation and regulation within the haemostatic system and fibrin clot microenvironment and introduce the emerging role of factor H as a modulator of coagulation. Finally, we discuss the potential impact of these protein interactions in diseases associated with factor H dysregulation or deficiency as well as evidence of coagulation dysfunction.
免疫补体和凝血系统是基于血液的蛋白水解级联反应，由特定途径的触发因素激活，基于蛋白质-蛋白质相互作用和酶促裂解反应。这些系统的激活通过特定的调节机制进行精细平衡和控制。补体和凝血系统通常被视为不同的系统，但具有共同的进化起源，并且已经报道了这些同源系统之间的几种相互作用。这种补体与凝血的相互作用可影响两个系统中的激活、放大和调节功能。在本综述中，我们总结了关于促成补体替代途径激活和调节的凝血因子的文献，并强调了补体替代途径调节因子H与几种凝血因子的分子相互作用。我们提出了一种机制，其中因子H与凝血因子的相互作用可能有助于止血系统和纤维蛋白凝块微环境中的补体和凝血激活及调节，并介绍了因子H作为凝血调节剂的新作用。最后，我们讨论了这些蛋白质相互作用在与因子H失调或缺乏相关的疾病中的潜在影响以及凝血功能障碍的证据。
