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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Journal ArticleDOI
z-VAD-fmk augmentation of TNFα-stimulated neutrophil apoptosis is compound specific and does not involve the generation of reactive oxygen species
TL;DR: Data suggest that TNF alpha-induced apoptosis in neutrophils is fully caspase dependent and uses a mitochondrial-independent pathway and that the proapoptotic effects of z-VAD-fmk are compound specific and ROS independent.
Journal ArticleDOI
Blockade of class IA phosphoinositide 3-kinase in neutrophils prevents NADPH oxidase activation- and adhesion-dependent inflammation.
TL;DR: It is concluded that class IA PI3K serves as a nodal point regulating CD11b/CD18-integrin-dependent PMN adhesion and activation of NADPH oxidase, and leads to oxidant production at sites of PMNAdhesion, and the resultant lung microvascular injury in mice.
Journal ArticleDOI
The diadenosine polyphosphates Ap3A and Ap4A and adenosine triphosphate interact with granulocyte-macrophage colony-stimulating factor to delay neutrophil apoptosis: implications for neutrophil: platelet interactions during inflammation
TL;DR: Because ATP, Ap3A, and AP4A may be secreted from activated platelets, these observations suggest that platelet-derived products, perhaps acting in combination with endothelial-derived or immune cell-derived cytokines, can regulate neutrophil function during certain types of inflammation.
Journal ArticleDOI
Induction of Bim limits cytokine-mediated prolonged survival of neutrophils.
TL;DR: A functional role for Bim is demonstrated in the regulation of neutrophil apoptosis and it is suggested that GM-CSF and other neutrophils hematopoietins initiate a proapoptotic counterregulation that involves upregulation of Bim.
Journal ArticleDOI
Alternative functions for TRAIL receptors in eosinophils and neutrophils.
Isabelle Daigle,Hans-Uwe Simon +1 more
TL;DR: In contrast to tumour cells, TRAIL does not induce apoptosis in granulocytes but rather induces survival in eosinophils from approximately 50% of the donors, and may limit cytokine-mediated antiapoptosis under certain inflammatory conditions.