Preventing the NET negative in primary graft dysfunction.
Preventing the NET negative in primary graft dysfunction.
复制标题
预防原发性移植物功能障碍中的 NET 阴性。
DOI：
10.1164/rccm.201412-2218ed
复制
发表时间：
2015
影响因子：
24.7
通讯作者：
Shilling,RebeccaA
中科院分区：
文献类型：
--
作者：
Emtiazjoo,Amir;Shilling,RebeccaA
原发性移植物功能障碍（PGD）是肺移植后缺血/再灌注损伤引发的急性肺损伤的一种形式。它影响10-35%的肺移植受者，是肺移植后早期发病和死亡的主要原因（1）。此外，PGD与慢性肺移植物功能障碍的风险增加有关，这是肺移植后晚期死亡的主要原因（2）。先前的研究已经提出了几个基于供体，受体和手术变量的PGD发展的风险因素（3）。PGD的发病机制尚不清楚。肺移植后缺血/再灌注损伤引发的炎症级联反应最终导致中性粒细胞流入肺部，已被认为是PGD发展的潜在病因（4）。由于PGD的发病机制尚不清楚，且缺乏任何既定的治疗方法，因此表征导致PGD的细胞和分子途径以开发靶向治疗至关重要。在本期杂志中，Sayah及其同事（pp. 455-463）提供了证据表明，中性粒细胞胞外陷阱（NET）在缺血/再灌注损伤后发展，并且募集依赖于血小板（5）。此外，他们发现与未接受PGD的受试者相比，接受PGD的人肺移植受者支气管肺泡灌洗液中的NET增加。有趣的是，在原位肺移植的小鼠模型中，使用抗血小板剂预防NET形成或使用DNA酶I破坏肺泡内NET可以保护PGD。先前在动物模型中的研究表明，中性粒细胞在移植物再灌注后的炎症反应中发挥作用，并发现破坏中性粒细胞浸润可以减少移植后的肺损伤（4，6）。中性粒细胞浸润和活化的后果之一可以是NET的形成，即挤出物，
Primary graft dysfunction (PGD) is a form of acute lung injury triggered by ischemia/reperfusion injury after lung transplantation. It affects 10-35% of lung allograft recipients and is the major cause of early morbidity and mortality after lung transplant (1). In addition, PGD has been associated with an increased risk of chronic lung allograft dysfunction, which is the major cause of late mortality after lung transplantation (2). Prior studies have proposed several risk factors for the development of PGD based on the donor, recipient, and surgical variables (3). The pathogenesis of PGD is not well understood. An inflammatory cascade initiated by ischemia/reperfusion injury after lung transplant, which ultimately leads to an influx of neutrophils into the lungs, has been suggested as the underlying etiology of the development of PGD (4). Given the unclear pathogenesis and lack of any established therapy for PGD, it is crucial to characterize the cellular and molecular pathways leading to PGD to develop targeted therapies. In this issue of the Journal, Sayah and colleagues (pp. 455-463) present evidence that neutrophil extracellular traps (NETs) develop after ischemia/reperfusion injury, and recruitment is dependent on platelets (5). Further, they find increased NETs in the bronchoalveolar lavage of human lung transplant recipients with PGD compared with subjects without PGD. Interestingly, the prevention of NET formation using an antiplatelet agent or intraalveolar disruption of NETs using DNase I protects against PGD in a mouse model of orthotopic lung transplant.Previous studies in animal models have suggested a role for neutrophils in the inflammatory response after graft reperfusion and found that disrupting neutrophil infiltration can reduce lung injury after transplant (4, 6). One of the consequences of neutrophil infiltration and activation can be the formation of NETs, extrusions