title: Matters of life and death. How neutrophils die or survive along NET release and is "NETosis" = necroptosis?
abstract: Neutrophil extracellular trap (NET) formation is a hallmark of many disorders that involve neutrophil recruitment, tissue damage, and inflammation. As NET formation is often associated with neutrophil death, the term "NETosis" has become popular. Upon discovery that neutrophils may survive NET release, apparent misnomers, such as "vital NETosis," have been proposed. Meanwhile, it has become obvious that certain stimuli can trigger neutrophil necroptosis, a process associated with NET-like chromatin release. Here, we discuss the relationship between NET release and neutrophil death in view highlighting that many assays used in the field do not properly distinguish between the two. An updated nomenclature is needed replacing the term "NETosis" to meet the growing variety of settings leading to chromatin release with and without neutrophil death. Dissecting which triggers of NET release involve which signaling pathway will help to define drugable molecular targets that inhibit NET release and/or neutrophil necrosis in specific disorders.
authors.affiliation: Medizinische Klinik and Poliklinik IV, Ludwig-Maximilians Universität München, Klinikum der Universität München-Innenstadt, Ziemssenstr. 1, 80336, Muenchen, Germany.
authors.forename: Jyaysi
authors.initials: J
authors.lastname: Desai
authors.affiliation: Medizinische Klinik and Poliklinik IV, Ludwig-Maximilians Universität München, Klinikum der Universität München-Innenstadt, Ziemssenstr. 1, 80336, Muenchen, Germany.
authors.forename: Shrikant R
authors.initials: SR
authors.lastname: Mulay
authors.affiliation: Medizinische Klinik and Poliklinik IV, Ludwig-Maximilians Universität München, Klinikum der Universität München-Innenstadt, Ziemssenstr. 1, 80336, Muenchen, Germany.
authors.forename: Daigo
authors.initials: D
authors.lastname: Nakazawa
authors.affiliation: Medizinische Klinik and Poliklinik IV, Ludwig-Maximilians Universität München, Klinikum der Universität München-Innenstadt, Ziemssenstr. 1, 80336, Muenchen, Germany. hjanders@med.uni-muenchen.de.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Anders
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D065206:Extracellular Traps / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D009336:Necrosis / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D011494:Protein Kinases / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
chemical_list: C570693:MLKL protein, human; D011494:Protein Kinases; C119705:RIPK3 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases
keywords: Gout; Histones; Host defense; Infection; Regulated necrosis; Sterile inflammation