Recent progress in the mechanistic understanding of NET formation in neutrophils. (11th June 2021)

• Record Type: Journal Article
• Authors: Liu, Ming‐Lin; Lyu, Xing; Werth, Victoria P.
• Is Part Of: FEBS journal. Volume 289:Number 14(2022)
• Page Start: 3954
• Page End: 3966
• Publication Date: 2021-06-11
• Subjects: chromatin decondensation -- NET formation -- NETosis -- neutrophils -- nuclear envelope rupture -- plasma membrane rupture; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.16036
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : Neutrophils are the most abundant circulating white blood cells and one of the major cell types of the innate immune system. Neutrophil extracellular traps (NETs) are a result of the extracellular release of nuclear chromatin from the ruptured nuclear envelope and plasma membrane. The externalized chromatin is an ancient defense weapon for animals to entrap and kill microorganisms in the extracellular milieu, thus protecting animals ranging from lower invertebrates to higher vertebrates. Although the externalized chromatin has the advantage of acting as anti‐infective to protect against infections, extracellular chromatin might be problematic in higher vertebrate animals as they have an adaptive immune system that can trigger further immune or autoimmune responses. NETs and their associated nuclear and/or cytoplasmic components may induce sterile inflammation, immune, and autoimmune responses, leading to various human diseases. Though important in human pathophysiology, the cellular and molecular mechanisms of NET formation (also called NETosis) are not well understood. Given that nuclear chromatin forms the backbone of NETs, the nucleus is the root of the nuclear DNA extracellular traps. Thus, nuclear chromatin decondensation, along with the rupture of nuclear envelope and plasma membrane, is required for nuclear chromatin extracellular release and NET formation. So far, most of the literature focuses on certain signaling pathways, which are involved in NET formation but without explanation of cellular events and morphological changes described above. Here, we have summarized emerging evidence and discuss new mechanistic understanding, with our perspectives, in NET formation in neutrophils. Abstract : The nucleus is the root of nuclear DNA extracellular traps in neutrophils. Nuclear envelope rupture is required for chromatin release and extracellular NET formation. Several recent works indicate that kinase‐mediated nuclear lamina disassembly is crucial to nuclear envelope rupture which enhances nuclear entry of decondensation enzymes, nuclear chromatin decondensation, and extracellular release for NET formation. The new mechanistic understanding is helpful for identification of molecular targets to control NET formation.