The role of extracellular traps in ischemia reperfusion injury

Abstract

In response to strong signals, several types of immune cells release extracellular traps (ETs), which are web-like structures consisting of DNA decorated with various protein substances. This process is most commonly observed in neutrophils. Over the past two decades, ET formation has been recognized as a unique mechanism of host defense and pathogen destruction. However, the role of ETs in sterile inflammation has only been studied extensively in recent years. Ischemia reperfusion injury (IRI) is a type of sterile inflammatory injury. Several studies have reported that ETs have an important role in IRI in various organs. In this review, we describe the release of ETs by various types of immune cells and focus on the mechanism underlying the formation of neutrophil ETs (NETs). In addition, we summarize the role of ETs in IRI in different organs and their effects on tumors. Finally, we discuss the value of ETs as a potential therapeutic target for organ IRI and present possible challenges in conducting studies on IRI-related ETs as well as future research directions and prospects.

Identification of renal ischemia reperfusion injury subtypes and predictive strategies for delayed graft function and graft survival based on neutrophil extracellular trap-related genes

“…In addition to capturing and killing microorganisms causing infectious diseases, NETs are also involved in the occurrence and development of non-infectious diseases, including cancer ( 28 ), autoimmune diseases ( 29 , 30 ), thrombosis ( 31 ), and sterile inflammatory tissue injury ( 32 ). Among them, renal IRI is a typical type of sterile inflammatory injury in which NETs play an important role ( 33 , 34 ). Studies have shown that inhibition of NET formation or promotion of NET degradation by PAD4 inhibitor or DNase I can improve renal IRI ( 16 , 35 ).…”

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

“…There is gathering evidence that neutrophils deliver inflammatory molecules using a potent process that promotes IRI in many transplanted organs including the liver ( 1 ). For reasons that are not yet clear, some but not all neutrophils can expel nuclear and mitochondrial DNA fibers that are bound with inflammatory cytokines, proteolytic enzymes, and histones.…”

“…For reasons that are not yet clear, some but not all neutrophils can expel nuclear and mitochondrial DNA fibers that are bound with inflammatory cytokines, proteolytic enzymes, and histones. These extracellular DNA fibers, known as neutrophil extracellular traps (NETs), were first reported to trap and kill pathogens ( 2 ), but can cause parenchymal tissue damage in the absence of observable infection ( 1 ). Most investigation has focused on elucidating the signals that promote NETosis.…”

The Formation of NETs and Their Mechanism of Promoting Tumor Metastasis

“…To date, two main forms of NETs release have been reported [2,3,[5][6][7][8][9][10][11], namely, lytic NETosis or suicidal NETosis and nonlytic NET formation or vital NET formation [6,[12][13][14][15]. Suicidal NETosis is a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent death process characterized by nuclear and granular membrane disintegration, chromatin decondensation, and the release of chromatin decorated with granular proteins and cell rupture.…”