Department of Organ Transplantation, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.
The Transplantation Insititute of Hainan Medical University, Haikou, Hainan, China.
Xenotransplantation. 2020 Sep;27(5):e12618. doi: 10.1111/xen.12618. Epub 2020 Sep 17.
Xenotransplantation may be an alternative source of organs for patients with end-stage organ failure, but problems remain to be overcome. Five factors that are problematic are (a) a sustained systemic inflammatory response in the xenograft recipient, (b) thrombotic microangiopathy and disseminated intravascular coagulation, (c) ischemia-reperfusion injury, (d) complement activation, and (e) vascular endothelial cell injury. In xenotransplantation, histones, which are positively charged proteins, are released into the extracellular space from damaged and activated cells, cause cell and tissue damage, and act as danger/damage-associated molecular patterns (DAMPs) that mediate inflammation, coagulation disorders, an immune response, and cytotoxicity. We have previously demonstrated that serum histones increase after pig-to-baboon organ transplantation and infection. Treatment of the recipient with tocilizumab (interleukin-6 receptor blockade) reduces the level of serum histones and C-reactive protein. In this review, the potential role of extracellular histones in xenotransplantation is discussed, and we briefly summarize the relationship between extracellular histones and the inflammatory response, coagulation dysfunction, ischemia-reperfusion injury, the complement system, and vascular endothelial cell injury.
异种移植可能是治疗终末期器官衰竭患者的一种替代器官来源，但仍存在需要克服的问题。有五个方面存在问题：（a）异种移植物受者持续的全身炎症反应；（b）血栓性微血管病和弥散性血管内凝血；（c）缺血再灌注损伤；（d）补体激活；以及（e）血管内皮细胞损伤。在异种移植中，带正电荷的蛋白质组蛋白从受损和激活的细胞释放到细胞外空间，导致细胞和组织损伤，并作为危险/损伤相关分子模式（DAMPs），介导炎症、凝血障碍、免疫反应和细胞毒性。我们之前已经证明，在猪到狒狒器官移植和感染后，血清组蛋白增加。用托珠单抗（白细胞介素-6 受体阻断剂）治疗受者可降低血清组蛋白和 C 反应蛋白的水平。在这篇综述中，讨论了细胞外组蛋白在异种移植中的潜在作用，并简要总结了细胞外组蛋白与炎症反应、凝血功能障碍、缺血再灌注损伤、补体系统和血管内皮细胞损伤之间的关系。
