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. 2019;6(1):78-89.
doi: 10.1007/s40472-019-0230-4. Epub 2019 Jan 29.

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

Kojiro Nakamura  1 , Shoichi Kageyama  1 , Jerzy W Kupiec-Weglinski  1
Affiliations

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

Kojiro Nakamura et al. Curr Transplant Rep. 2019.

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: homeostasis recovery; liver ischemia-reperfusion injury; neutrophil; neutrophil extracellular traps; reverse migration.

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Conflict of interest statement

Conflict of Interest Kojiro Nakamura, Shoichi Kageyama, and Jerzy W. Kupiec-Weglinski declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Putative mechanisms of neutrophil recruitment in liver ischemia-reperfusion injury. a Liver-resident Kupffer cells and liver sinusoidal endothelial cells (LSECs) sense initial danger-associated molecular patterns (DAMPs) via pattern recognition receptors (PRRs) to trigger intercellular adhesion molecule-1 (ICAM-1) expression on endothelial cells and neutrophil adhesion by integrin αMβ2 (Mac-1) signaling. b Neutrophils move on the LSECs luminal side toward the damaged site, guided by Kupffer cell-derived chemokine (CXCL1/CXCL2) gradient. c Neutrophils detect mitochondrial N-formyl peptides (FMIT) via formyl peptide receptor 1 (FPR1) and migrate underneath LSECs toward the injury site. d Neutrophils express and secret matrix metalloproteinase 9 (MMP9) to degrade extracellular matrix (ECM) during migration
See this image and copyright information in PMC

References

    1. Dutkowski P, Linecker M, DeOliveira ML, Mullhaupt B, Clavien PA. Challenges to liver transplantation and strategies to improve outcomes. Gastroenterology. 2015;148(2):307–323. doi: 10.1053/j.gastro.2014.08.045. - DOI - PubMed
    1. Busuttil RW, Tanaka K. The utility of marginal donors in liver transplantation. Liver Transpl. 2003;9(7):651–663. doi: 10.1053/jlts.2003.50105. - DOI - PubMed
    1. Zhai Y, Petrowsky H, Hong JC, Busuttil RW, Kupiec-Weglinski JW. Ischaemia-reperfusion injury in liver transplantation--from bench to bedside. Nat Rev Gastroenterol Hepatol. 2013;10(2):79–89. doi: 10.1038/nrgastro.2012.225. - DOI - PMC - PubMed
    1. Selzner M, Selzner N, Jochum W, Graf R, Clavien PA. Increased ischemic injury in old mouse liver: an ATP-dependent mechanism. Liver Transpl. 2007;13(3):382–390. doi: 10.1002/lt.21100. - DOI - PubMed
    1. Guan LY, Fu PY, Li PD, Li ZN, Liu HY, Xin MG, Li W. Mechanisms of hepatic injury and protective effects of nitric oxide. World J Gastrointest Surg. 2014;6(7):122–128. doi: 10.4240/wjgs.v6.i7.122. - DOI - PMC - PubMed