Complement-targeting therapeutics for ischemia-reperfusion injury in transplantation and the potential for ex vivo delivery.
Complement-targeting therapeutics for ischemia-reperfusion injury in transplantation and the potential for ex vivo delivery.
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DOI：
10.3389/fimmu.2022.1000172
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
器官短缺和不断扩大的候补名单导致边缘器官的利用率增加。所有供体器官在移植过程中都会受到不同程度的 IRI 影响。扩展标准器官，包括来自老年捐献者的器官和循环死亡后捐献的器官，特别容易受到缺血再灌注损伤（IRI）。补体级联在介导 IRI 中的参与已得到广泛研究。补体在 IRI 的传播和随后适应性免疫元件的招募中发挥着至关重要的作用。在临床前模型中，该通路各个点的补体抑制已被证明可以减轻 IRI 并最大程度地减少未来免疫介导的损伤。最近推出的离体机器灌注平台为治疗干预提供了理想的窗口。在这里，我们回顾了补体在器官系统 IRI 中的作用，并强调了供体器官离体机器保存过程中干预的潜在治疗靶点。
Organ shortages and an expanding waitlist have led to increased utilization of marginal organs. All donor organs are subject to varying degrees of IRI during the transplant process. Extended criteria organs, including those from older donors and organs donated after circulatory death are especially vulnerable to ischemia-reperfusion injury (IRI). Involvement of the complement cascade in mediating IRI has been studied extensively. Complement plays a vital role in the propagation of IRI and subsequent recruitment of the adaptive immune elements. Complement inhibition at various points of the pathway has been shown to mitigate IRI and minimize future immune-mediated injury in preclinical models. The recent introduction of ex vivo machine perfusion platforms provides an ideal window for therapeutic interventions. Here we review the role of complement in IRI by organ system and highlight potential therapeutic targets for intervention during ex vivo machine preservation of donor organs.
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