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

Nakamura, Kojiro; Kageyama, Shoichi; Kupiec-Weglinski, Jerzy W.

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.