Peculiarities of cell death mechanisms in neutrophils.
Barbara Geering,Hans-Uwe Simon +1 more
TLDR
The current and emerging models of neutrophil cell death mechanisms are reviewed with a focus on neutrophils peculiarities, including mitochondrial death pathway, and pharmacological intervention of inflammation.Abstract:
Analyses of neutrophil death mechanisms have revealed many similarities with other cell types; however, a few important molecular features make these cells unique executors of cell death mechanisms. For instance, in order to fight invading pathogens, neutrophils possess a potent machinery to produce reactive oxygen species (ROS), the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Evidence is emerging that these ROS are crucial in the execution of most neutrophil cell death mechanisms. Likewise, neutrophils exhibit many diverse granules that are packed with cytotoxic mediators. Of those, cathepsins were recently shown to activate pro-apoptotic B-cell lymphoma-2 (Bcl-2) family members and caspases, thus acting on apoptosis regulators. Moreover, neutrophils have few mitochondria, which hardly participate in ATP synthesis, as neutrophils gain energy from glycolysis. In spite of relatively low levels of cytochrome c in these cells, the mitochondrial death pathway is functional. In addition to these pecularities defining neutrophil death pathways, neutrophils are terminally differentiated cells, hence they do not divide but undergo apoptosis shortly after maturation. The initial trigger of this spontaneous apoptosis remains to be determined, but may result from low transcription and translation activities in mature neutrophils. Due to the unique biological characteristics of neutrophils, pharmacological intervention of inflammation has revealed unexpected and sometimes disappointing results when neutrophils were among the prime target cells during therapy. In this study, we review the current and emerging models of neutrophil cell death mechanisms with a focus on neutrophil peculiarities.read more
Citations
More filters
Journal ArticleDOI
Tear Fluid Extracellular DNA: Diagnostic and Therapeutic Implications in Dry Eye Disease
Sapna Tibrewal,Joy Sarkar,Sarmad Jassim,Sonal Gandhi,Snehal Sonawane,Shweta Chaudhary,Yong Soo Byun,Yair Ivanir,Joelle A. Hallak,John H. Horner,Martin Newcomb,Sandeep Jain +11 more
TL;DR: A novel therapeutic approach for managing DED may be to measure eDNA abundance in tear fluid with the PicoGreen dye assay and reduce excessive amounts with DNase I eyedrops.
Journal ArticleDOI
Necrostatin-1 enhances the resolution of inflammation by specifically inducing neutrophil apoptosis
Hongyu Jie,Yi He,Xuechan Huang,Qingyou Zhou,Yanping Han,Yanping Han,Xing Li,Yongkun Bai,Erwei Sun +8 more
TL;DR: Nec-1 markedly enhanced the resolution of established neutrophil-dependent inflammation in LPS-induced acute lung injury in mice and suggested that Nec-1 may have potential roles for the treatment of diseases with increased or persistent inflammatory responses.
Journal ArticleDOI
Nox2-derived oxidative stress results in inefficacy of antibiotics against post-influenza S. aureus pneumonia.
Keer Sun,Keer Sun,Vijaya Kumar Yajjala,Christopher Bauer,Geoffrey A. Talmon,Karl J. Fischer,Tammy Kielian,Dennis W. Metzger +7 more
TL;DR: In this paper, the authors show that combination treatment of antibiotic and NADPH oxidase inhibitor significantly improved animal survival from S. aureus coinfection and showed that Nox2-induced lung damage was not associated with aggravated inflammatory cytokine response or cell infiltration but rather caused by reduced survival of myeloid cells.
Posted ContentDOI
Genome-wide Analysis of Differential Transcriptional and Epigenetic Variability Across Human Immune Cell Types
Simone Ecker,Lu Chen,Lu Chen,Vera Pancaldi,Frederik Otzen Bagger,Frederik Otzen Bagger,Frederik Otzen Bagger,José M. Fernández,Enrique Carrillo-de Santa Pau,David Juan,Alice L. Mann,Stephen Watt,Francesco Paolo Casale,Nikos Sidiropoulos,Nicolas Rapin,Angelika Merkel,Henk Stunnenberg,Oliver Stegle,Mattia Frontini,Mattia Frontini,Mattia Frontini,Kate Downes,Kate Downes,Tomi Pastinen,Taco W. Kuijpers,Daniel Rico,Alfonso Valencia,Stephan Beck,Nicole Soranzo,Nicole Soranzo,Dirk S. Paul,Dirk S. Paul +31 more
TL;DR: In neutrophils, genes with hypervariable expression were found to be implicated in key immune pathways and to associate with cellular properties and environmental exposure, and Neutrophil-specific DNA methylation hypervariable sites were enriched at dynamic chromatin regions and active enhancers.
Journal ArticleDOI
Non-apoptotic functions of caspases in myeloid cell differentiation.
Stéphanie Solier,Michaela Fontenay,William Vainchenker,Nathalie Droin,Eric Solary,Eric Solary +5 more
TL;DR: Questions remain on how these proteases are activated in myeloid cell lineages, which target proteins are cleaved, whereas other are protected from proteolysis, the precise role of cleaved proteins in cell differentiation and functions, and the link between these non-apoptotic functions of caspases and the death of these diverse cell types.
References
More filters
Journal ArticleDOI
Neutrophil extracellular traps kill bacteria
Volker Brinkmann,Ulrike Reichard,Christian Goosmann,Beatrix Fauler,Yvonne Uhlemann,David S. Weiss,Yvette Weinrauch,Yvette Weinrauch,Arturo Zychlinsky +8 more
TL;DR: It is described that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria, which degrade virulence factors and kill bacteria.
Journal ArticleDOI
Classification of cell death: recommendations of the Nomenclature Committee on Cell Death
Guido Kroemer,Guido Kroemer,Guido Kroemer,Lorenzo Galluzzi,Lorenzo Galluzzi,Lorenzo Galluzzi,Peter Vandenabeele,John M. Abrams,Emad S. Alnemri,Eric H. Baehrecke,Mikhail V. Blagosklonny,Wafik S. El-Deiry,Pierre Golstein,Pierre Golstein,Douglas R. Green,Michael O. Hengartner,Richard A. Knight,Sharad Kumar,Stuart A. Lipton,Stuart A. Lipton,Stuart A. Lipton,Walter Malorni,Gabriel Núñez,Marcus E. Peter,Juerg Tschopp,Junying Yuan,Mauro Piacentini,Boris Zhivotovsky,Gerry Melino,Gerry Melino +29 more
TL;DR: This study details the 2009 recommendations of the NCCD on the use of cell death-related terminology including ‘entosis’, ‘mitotic catastrophe”,’ ‘necrosis‚ ‘necroptosis‚’ and ‘pyroptotic’.
Journal ArticleDOI
Role of reactive oxygen species (ROS) in apoptosis induction
TL;DR: The role of ROS in the regulation of apoptosis, especially in inflammatory cells, is focused on, with particular attention to mitochondria.
Journal ArticleDOI
Novel cell death program leads to neutrophil extracellular traps
Tobias A. Fuchs,Ulrike Abu Abed,Christian Goosmann,Robert Hurwitz,Ilka Schulze,Volker Wahn,Yvette Weinrauch,Volker Brinkmann,Arturo Zychlinsky +8 more
TL;DR: This novel ROS-dependent death allows neutrophils to fulfill their antimicrobial function, even beyond their lifespan.
Journal ArticleDOI
Chronic granulomatous disease. Report on a national registry of 368 patients.
Jerry A. Winkelstein,Mary C. Marino,Richard B. Johnston,John Boyle,John T. Curnutte,John I. Gallin,Harry L. Malech,S.M. Holland,Hans D. Ochs,Paul G. Quie,Rebecca H. Buckley,Charles B. Foster,S. J. Chanock,Howard B. Dickler +13 more
TL;DR: A registry of United States residents with chronic granulomatous disease (CGD) was established in 1993 in order to estimate the minimum incidence of this uncommon primary immunodeficiency disease and characterize its epidemiologic and clinical features.