Peculiarities of cell death mechanisms in neutrophils.
Barbara Geering,Hans-Uwe Simon +1 more
Reads0
Chats0
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
Diverse novel functions of neutrophils in immunity, inflammation, and beyond
TL;DR: Novel findings on versatile functions of neutrophils are summarized, which appear to be related to their unique ability to release neutrophil extracellular traps even in the absence of pathogens.
Journal ArticleDOI
Resolution of inflammation: an integrated view
TL;DR: This review integrates the key molecular and cellular mechanisms of resolution and describes how abrogation of chemokine signalling blocks continued neutrophil tissue infiltration and how apoptotic neutrophils attract monocytes and macrophages to induce their clearance.
Journal ArticleDOI
ROS production in phagocytes: why, when, and where?
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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
More filters
Journal ArticleDOI
Molecular analysis of neutrophil spontaneous apoptosis reveals a strong role for the pro-apoptotic BH3-only protein Noxa
Susanne Kirschnek,Juliane Vier,Sanjivan Gautam,Tobias Frankenberg,S Rangelova,P Eitz-Ferrer,P Eitz-Ferrer,Francesca Grespi,Eleonora Ottina,Andreas Villunger,Hans Häcker,Georg Häcker +11 more
TL;DR: Apoptosis regulated by Bim- and Noxa-driven loss of Mcl-1 is thus the final step in neutrophil differentiation, required for the termination of neutrophils function and neutrophIL-dependent inflammation.
Journal ArticleDOI
Host defenses against respiratory infection
TL;DR: New opportunities for the therapeutic augmentation of defenses are emerging that may be particularly helpful in the care of immunocompromised patients.
Journal ArticleDOI
Apoptotic Neutrophils Release Macrophage Migration Inhibitory Factor upon Stimulation with Tumor Necrosis Factor-α
TL;DR: It is demonstrated that mature blood and tissue neutrophils constitutively express MIF as a cytosolic protein not associated with azurophil granules, suggesting that this transporter system is activated during neutrophil apoptosis.
Journal ArticleDOI
Rapid induction of neutrophil apoptosis by sulfasalazine: implications of reactive oxygen species in the apoptotic process
TL;DR: Analysis of the effect of sulfasalazine on neutrophil apoptosis in vitro provided pharmacological evidence that the phosphorylation of tyrosine kinase and protein kinase A and generation of reactive oxygen species are involved in SSZ‐mediated neutrophils apoptosis.
Journal ArticleDOI
Autophagic-Like Cell Death in Neutrophils Induced by Autoantibodies
TL;DR: Interestingly, human intravenous immunoglobulin (IVIg) preparations contain natural anti-Siglec-9 autoantibodies, which are able to ligate SigleC-9 on neutrophils and induce autophagic-like cell death in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and some other survival cytokines.