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Silver nanoparticles rapidly induce atypical human neutrophil cell death by a process involving inflammatory caspases and reactive oxygen species and induce neutrophil extracellular traps release upon cell adhesion . Author links open the author workspace.

Abstract : Inflammation is one of the major toxic effects reported in response to in vitro or in vivo nanoparticle (NP) exposure. Among engineered NPs, silver nanoparticles (AgNPs) are very attractive for the development of therapeutic strategies, especially because of their antimicrobial properties. In humans, neutrophils, key players in inflammation, are the most abundant blood leukocytes that spontaneously undergo apoptosis, a central cell death mechanism regulating inflammation. The aim of this study was to evaluate the effect of AgNPs on neutrophil apoptosis. Transmission electronic microscopy reveals that AgNPs rapidly penetrate inside neutrophils. AgNPs induced atypical cell death where the cell volume increased and the cell surface expression of CD16 remained unaltered unlike apoptotic neutrophils where cell shrinkage and loss of CD16 are typically observed. The AgNP-induced atypical cell death is distinct from necrosis and reversed by a pancaspase inhibitor or by inhibitors of the inflammatory caspase-1 and caspase-4. In addition, AgNPs induced IL-1β production inhibited by caspase-1 and caspase-4 inhibitors and also induced caspase-1 activity. Reactive oxygen species (ROS) production was increased by AgNPs and the atypical cell death was inhibited by the antioxidant n-acetylcysteine. Under similar experimental conditions, adhesion of neutrophils leads to neutrophil extracellular trap (NET) release induced by AgNPs. However, this process was not reversed by caspase inhibitors. We conclude that AgNPs rapidly induced an atypical cell death in neutrophils by a mechanism involving caspase-1, -4 and ROS. However, in adherent neutrophils, AgNPs induced NET release and, therefore, are novel agents able to trigger NET release.
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https://hal-riip.archives-ouvertes.fr/pasteur-01352190
Contributor : Michel Courcelles <>
Submitted on : Friday, August 5, 2016 - 6:43:46 PM
Last modification on : Monday, October 8, 2018 - 5:44:05 PM

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Rafael Liz, Jean-Christophe Simard, Laurien Bruna Araújo Leonardi, Denis Girard. Silver nanoparticles rapidly induce atypical human neutrophil cell death by a process involving inflammatory caspases and reactive oxygen species and induce neutrophil extracellular traps release upon cell adhesion . Author links open the author workspace.. International Immunopharmacology, Elsevier, 2015, 28 (1), pp.616-25. ⟨10.1016/j.intimp.2015.06.030⟩. ⟨pasteur-01352190⟩

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