The Evolving Role of Neutrophils in Liver Transplant Ischemia-Reperfusion Injury

  • Kojiro Nakamura
  • Shoichi Kageyama
  • Jerzy W. Kupiec-WeglinskiEmail author
Immunology (R Fairchild , Editor)
Part of the following topical collections:
  1. Topical Collection on Immunology


Purpose of Review

Hepatic ischemia-reperfusion injury (IRI), an inevitable event during liver transplantation, represents a major risk factor for the primary graft dysfunction as well as the development of acute and chronic rejection. Neutrophils, along macrophages, are pivotal in the innate immune-driven liver IRI, whereas the effective neutrophil-targeting therapies remain to be established. In this review, we summarize progress in our appreciation of the neutrophil biology and discuss neutrophil-based therapeutic perspectives.

Recent Findings

New technological advances enable to accurately track neutrophil movements and help to understand molecular mechanisms in neutrophil function, such as selective recruitment to IR-stressed tissue, formation of neutrophil extracellular traps, or reverse migration into circulation. In addition to pro-inflammatory and tissue-destructive functions, immune regulatory and tissue-repairing phenotype associated with distinct neutrophil subsets have been identified.


Newly recognized and therapeutically attractive neutrophil characteristics warrant comprehensive preclinical and clinical attention to target IRI in transplant recipients.


Neutrophil Liver ischemia-reperfusion injury Homeostasis recovery Neutrophil extracellular traps Reverse migration 



Annexin A1


Acute respiratory distress syndrome


Adenosine triphosphate


Carbon tetrachloride


Danger-associated molecular patterns


Extracellular matrix


Mitochondrial N-formyl peptides


Formyl peptide receptor 1


Formyl peptide receptor 2


High mobility group box 1


Intercellular adhesion molecule-1


Ischemia-reperfusion injury


Liver sinusoidal endothelial cell


Liver transplantation


Integrin αMβ2


Matrix metalloproteinase




Nicotinamide adenine dinucleotide phosphate


Neutrophil extracellular trap


NOD-like receptor pyrin domain-containing-3


Protein-arginine deiminase 4


Pattern recognition receptor


Reactive oxygen species


Tissue inhibitor of metalloproteinase


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Kojiro Nakamura
    • 1
  • Shoichi Kageyama
    • 1
  • Jerzy W. Kupiec-Weglinski
    • 1
    Email author
  1. 1.The Dumont-UCLA Transplant Center, Department of Surgery, Division of Liver and Pancreas TransplantationDavid Geffen School of Medicine at University of CaliforniaLos AngelesUSA

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