The Role of Neutrophil NETosis in Organ Injury: Novel Inflammatory Cell Death Mechanisms
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REVIEW
The Role of Neutrophil NETosis in Organ Injury: Novel Inflammatory Cell Death Mechanisms Zhen Cahilog,1 Hailin Zhao,1 Lingzhi Wu,1 Azeem Alam,1 Shiori Eguchi,1 Hao Weng,2 and Daqing Ma 1,3
NETosis is a type of regulated cell death dependent on the formation of neutrophil extracellular traps (NET), where net-like structures of decondensed chromatin and proteases are produced by polymorphonuclear (PMN) granulocytes. These structures immobilise pathogens and restrict them with antimicrobial molecules, thus preventing their spread. Whilst NETs possess a fundamental anti-microbial function within the innate immune system under physiological circumstances, increasing evidence also indicates that NETosis occurs in the pathogenic process of other disease type, including but not limited to atherosclerosis, airway inflammation, Alzheimer’s and stroke. Here, we reviewed the role of NETosis in the development of organ injury, including injury to the brain, lung, heart, kidney, musculoskeletal system, gut and reproductive system, whilst therapeutic agents in blocking injuries induced by NETosis in its primitive stages were also discussed. This review provides novel insights into the involvement of NETosis in different organ injuries, and whilst potential therapeutic measures targeting NETosis remain a largely unexplored area, these warrant further investigation.
Abstract—
KEY WORDS: NETosis; neutrophil; organ injury; cell death; inflammation.
BACKGROUND Cell death is commonly segregated into necrosis and apoptosis; apoptosis being programmed cell death, 1
Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK 2 Department of Anesthesiology, Shanghai Fengxian District Central Hospital, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital South Campus, Fengxian District, Shanghai, China 3 To whom correspondence should be addressed at Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK. E-mail: [email protected]
for instance during development and physiological cellular turnover, whilst necrosis predominantly takes place in an unregulated manner [1]. NETosis, like necrosis, is a mode of cell death that involves the loss of membrane integrity. During NETosis, decondensation of chromatin is thought to be initiated by peptidyl arginine deiminase 4 (PAD4) [2]; its subsequent release together with granule contents is vital in the innate immune response to infection and inflammation. Recent studies suggest that NET formation is of central to pathogenesis of organ injury. This review will summarise the current understanding of the molecular mechanisms of NETosis and the therapeutic approaches under development targeting NET-induced organ injury.
0360-3997/20/0000-0001/0 # 2020 The Author(s). This article is an open access
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