Avoid being trapped by your liver: ischemia-reperfusion injury in liver transplant triggers S1P-mediated NETosis

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Abstract

Liver transplantation can be a life-saving treatment for end-stage hepatic disease. Unfortunately, some recipients develop ischemia-reperfusion injury (IRI) that leads to poor short- and long-term outcomes. Recent work has shown neutrophils contribute to IRI by undergoing NETosis, a form of death characterized by DNA ejection resulting in inflammatory extracellular traps. In this issue of the JCI, Hirao and Kojima et al. report that sphingosine-1-phosphate (S1P) expression induced by liver transplant–mediated IRI triggers NETosis. They also provide evidence that neutrophil expression of the carcinoembryonic antigen–related cell adhesion molecule-1 (CC1) long isoform inhibited NETosis by controlling S1P receptor–mediated autophagic flux. These findings suggest stimulating regulatory mechanisms that suppress NETosis could be used to prevent IRI.

Authors

Davide Scozzi, Andrew E. Gelman