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
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Diverse novel functions of neutrophils in immunity, inflammation, and beyond
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TL;DR: Examples of local ROS production, decreased degradation, signaling events, and potentially ROS‐sensitive functions are presented and the current limitations for quantitative spatiotemporal ROS detection are illustrated.
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Clearance of apoptotic neutrophils and resolution of inflammation
TL;DR: This review will highlight how the engulfment of apoptotic neutrophils by human phagocytes occurs, how heterogeneity of phagocyte populations influences efferocytosis signaling, and downstream consequences of effercytosis.
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The transcriptional landscape of αβ T cell differentiation
Michael Mingueneau,Taras Kreslavsky,Daniel H.D. Gray,Daniel H.D. Gray,Tracy Heng,Richard M. Cruse,Jeffrey Ericson,Sean C. Bendall,Matthew H. Spitzer,Garry P. Nolan,Koichi Kobayashi,Koichi Kobayashi,Harald von Boehmer,Diane Mathis,Christophe Benoist +14 more
TL;DR: It is found that early T cell commitment was driven by unexpectedly gradual changes, and transcripts newly identified as encoding candidate mediators of key transitions help define the 'known unknowns' of thymocyte differentiation.
References
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Cathepsin-cleaved Bid promotes apoptosis in human neutrophils via oxidative stress-induced lysosomal membrane permeabilization.
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Mycobacterium tuberculosis Promotes Apoptosis in Human Neutrophils by Activating Caspase-3 and Altering Expression of Bax/Bcl-xL Via an Oxygen-Dependent Pathway
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Apoptotic Pathways Are Inhibited by Leptin Receptor Activation in Neutrophils
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The role of the bone marrow in neutrophil clearance under homeostatic conditions in the mouse
Rebecca C. Furze,Sara M. Rankin +1 more
TL;DR: Evidence is provided that the bone marrow represents a major site of neutrophil clearance in mice and under noninflammatory conditions, circulating levels of neutrophic levels are regulated by granulocyte‐colony stimulating factor (G‐CSF), but not interleukin‐17.