Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at University of California, Los Angeles, California, USA.
Department of Surgery, Kyoto University, Kyoto.
Curr Opin Organ Transplant. 2019 Dec;24(6):687-693. doi: 10.1097/MOT.0000000000000709.
Although organ transplantation has become the standard life-saving strategy for patients with end-stage organ failure and those with malignancies, effective and safe therapeutic strategies to combat allograft loss remain to be established. With the emerging evidence suggesting the critical role of innate immunity in the mechanism of allograft injury, we summarize the latest understanding of macrophage-neutrophil cross-communication and discuss therapeutic prospects of their targeting in transplant recipients.
Macrophages and neutrophils contribute to the pathogenesis of early peritransplant ischemia-reperfusion injury and subsequent allograft rejection immune cascade, primarily by exacerbating inflammatory response and tissue damage. Noteworthy, recent advances enabled to elucidate multifaceted functions of innate immune cells, which are not only deleterious but may also prove graft-protective. Indeed, the efficacy of macrophage polarizing regimens or macrophage-targeted migration have been recognized to create graft-protective local environment. Moreover, novel molecular mechanisms in the neutrophil function have been identified, such as neutrophil extracellular traps, tissue-repairing capability, crosstalk with macrophages and T cells as well as reverse migration into the circulation.
As efficient strategies to manage allograft rejection and improve transplant outcomes are lacking, newly discovered, and therapeutically attractive innate immune cell functions warrant comprehensive preclinical and clinical attention.
目的综述：尽管器官移植已成为治疗终末期器官衰竭和恶性肿瘤患者的标准救生策略，但仍需建立有效和安全的治疗策略来对抗移植物失功。随着越来越多的证据表明固有免疫在移植物损伤机制中起着关键作用，我们总结了对巨噬细胞-中性粒细胞交叉通讯的最新理解，并讨论了靶向移植受者中这些细胞的治疗前景。
最近的发现：巨噬细胞和中性粒细胞通过加剧炎症反应和组织损伤，有助于移植前缺血再灌注损伤和随后的移植物排斥免疫级联的早期发病机制。值得注意的是，最近的进展使人们能够阐明固有免疫细胞的多方面功能，这些功能不仅具有破坏性，而且可能具有保护移植物的作用。事实上，已经认识到巨噬细胞极化方案或巨噬细胞靶向迁移的功效可以创造具有保护移植物的局部环境。此外，还发现了中性粒细胞功能的新分子机制，例如中性粒细胞胞外诱捕网、组织修复能力、与巨噬细胞和 T 细胞的串扰以及反向迁移到循环中。
总结：由于缺乏有效的管理移植物排斥和改善移植结果的策略，新发现的、具有治疗吸引力的固有免疫细胞功能需要得到全面的临床前和临床关注。
