期刊
CELL DEATH AND DIFFERENTIATION
卷 18, 期 9, 页码 1457-1469出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2011.75
关键词
apoptosis; autophagy; death signaling; inflammation; reactive oxygen species; neutrophilic granulocytes
资金
- Swiss National Science Foundation [310030_129640/1]
- Roche Research Foundation (Switzerland)
- L'Oreal - For Women In Science (Switzerland)
- Swiss National Science Foundation (SNF) [310030_129640] Funding Source: Swiss National Science Foundation (SNF)
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. Cell Death and Differentiation (2011) 18, 1457-1469; doi:10.1038/cdd.2011.75; published online 3 June 2011
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