Peculiarities of cell death mechanisms in neutrophils.
Barbara Geering,Hans-Uwe Simon +1 more
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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
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References
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Accelerated Neutrophil Apoptosis in Mice Lacking A1-a, a Subtype of the bcl-2–related A1 Gene
Azumi Hamasaki,Fujiro Sendo,Keiko Nakayama,Noriko Ishida,Izumi Negishi,Keiichi I. Nakayama,Shigetsugu Hatakeyama +6 more
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p38-MAPK Signals Survival by Phosphorylation of Caspase-8 and Caspase-3 in Human Neutrophils
Maria Alvarado-Kristensson,Fredrik Melander,Karin Leandersson,Lars Rönnstrand,Christer Wernstedt,Tommy Andersson +5 more
TL;DR: In this paper, the p38-mitogen-activated protein kinase (MAPK) associates to caspase-8 and caspases-3 during neutrophil apoptosis.
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TL;DR: It is demonstrated that the effect of GM-CSF on granulocyte cell death can be blocked by the tyrosine kinase inhibitor genistein, suggesting that increases in tyrosin phosphorylation are essential to inhibit cell death.
Journal ArticleDOI
Hypoxia prolongs neutrophil survival in vitro
Sharon Hannah,Kathryn Mecklenburgh,Irfan Rahman,Geoffrey J. Bellingan,Andrew P. Greening,Christopher Haslett,Edwin R. Chilvers +6 more
TL;DR: Hypoxia has a bcl‐2‐independent effect on neutrophil appoptosis that may adversely affect the clearance of these cells from an inflammatory focus.