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

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

Abstract

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.

Summary

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

Keywords

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

Abbreviations

AnxA1

Annexin A1

ARDS

Acute respiratory distress syndrome

ATP

Adenosine triphosphate

CCl4

Carbon tetrachloride

DAMPs

Danger-associated molecular patterns

ECM

Extracellular matrix

FMIT

Mitochondrial N-formyl peptides

FPR1

Formyl peptide receptor 1

FPR2

Formyl peptide receptor 2

HMGB1

High mobility group box 1

ICAM-1

Intercellular adhesion molecule-1

IRI

Ischemia-reperfusion injury

LSEC

Liver sinusoidal endothelial cell

LT

Liver transplantation

Mac1

Integrin αMβ2

MMP

Matrix metalloproteinase

MPO

Myeloperoxidase

NADPH

Nicotinamide adenine dinucleotide phosphate

NET

Neutrophil extracellular trap

NLRP3

NOD-like receptor pyrin domain-containing-3

PAD4

Protein-arginine deiminase 4

PRR

Pattern recognition receptor

ROS

Reactive oxygen species

TIMP

Tissue inhibitor of metalloproteinase

Notes

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.

References

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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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