Joshua M Diamond1, Christopher H Wigfield. 1. 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.
Abstract
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
Authors: A A Abbas; J M Diamond; C Chehoud; B Chang; J J Kotzin; J C Young; I Imai; A R Haas; E Cantu; D J Lederer; K C Meyer; R K Milewski; K M Olthoff; A Shaked; J D Christie; F D Bushman; R G Collman Journal: Am J Transplant Date: 2016-11-04 Impact factor: 8.086
Authors: Ciara M Shaver; Nancy Wickersham; J Brennan McNeil; Hiromasa Nagata; Adam Miller; Stuart R Landstreet; Jamie L Kuck; Joshua M Diamond; David J Lederer; Steven M Kawut; Scott M Palmer; Keith M Wille; Ann Weinacker; Vibha N Lama; Maria M Crespo; Jonathan B Orens; Pali D Shah; Chadi A Hage; Edward Cantu; Mary K Porteous; Gundeep Dhillon; John McDyer; Julie A Bastarache; Jason D Christie; Lorraine B Ware Journal: JCI Insight Date: 2018-01-25
Authors: Xiaoli Tian; He Sun; Amy-Jo Casbon; Edward Lim; Kevin P Francis; Judith Hellman; Arun Prakash Journal: Front Immunol Date: 2017-10-31 Impact factor: 7.561
Authors: Joshua A Blatter; Tsuyoshi Takahashi; Brigitte Mittler; Ruben G Nava; Varun Puri; Daniel Kreisel; David Wang Journal: Transplant Direct Date: 2020-01-13