Diamond Joshua M, Wigfield Christopher H
aPulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania bSection of Cardiothoracic Surgery, University of Chicago, Chicago, Illinois, USA.
Curr Opin Organ Transplant. 2013 Oct;18(5):518-23. doi: 10.1097/MOT.0b013e3283651994.
Primary graft dysfunction (PGD), a form of acute lung injury after lung transplantation, has a significant impact on clinical outcomes after lung transplantation. This potentially reversible graft impairment occurs after ischemia-reperfusion injury. This review describes the expanding body of literature evaluating the central role of innate immune activation, nonadaptive responses and dysregulation in the development of PGD after lung transplant.
The innate immune system, highlighted by Toll-like receptor pathways and neutrophil migration and influx, plays an important role in the initiation and propagation of ischemia-reperfusion injury. Recent plasma biomarker and gene association studies have identified several genes and proteins composing innate immune pathways to be associated with PGDs. Long pentraxin-3 and Toll-like receptors, as well as inflammasomes and Toll-interacting protein, are associated with the development of PGD after lung transplantation.
Innate immune pathways are involved in the development of PGD and may provide attractive targets for therapies. It may be possible to prevent or treat PGD, as well as to allow pre-transplant PGD risk stratification. To improve understanding of the mechanisms behind clinical risk factors for PGD will require further in-depth correlation of donor-specific and recipient-related triggers of nonadaptive immune responses.
原发性移植肺功能障碍（PGD）是肺移植后急性肺损伤的一种形式，对肺移植后的临床结局有重大影响。这种潜在可逆的移植肺损伤发生在缺血再灌注损伤之后。本综述描述了越来越多的文献，这些文献评估了固有免疫激活、非适应性反应和失调在肺移植后PGD发生过程中的核心作用。
以Toll样受体途径以及中性粒细胞迁移和流入为突出表现的固有免疫系统，在缺血再灌注损伤的起始和传播中起重要作用。最近的血浆生物标志物和基因关联研究已经确定了几个构成固有免疫途径的基因和蛋白质与PGD相关。长五聚体蛋白-3和Toll样受体，以及炎性小体和Toll相互作用蛋白，都与肺移植后PGD的发生有关。
固有免疫途径参与了PGD的发生，可能为治疗提供有吸引力的靶点。预防或治疗PGD，以及进行移植前PGD风险分层或许是可行的。为了更好地理解PGD临床危险因素背后的机制，需要进一步深入关联供体特异性和受体相关的非适应性免疫反应触发因素。
