Zinc oxide nanoparticles delay human neutrophil apoptosis by a de novo protein synthesis-dependent and reactive oxygen species-independent mechanism.
Inflammation is one of the major toxic effects reported in the literature following nanoparticle (NP) exposure. Knowing the importance of neutrophils to orchestrate inflammation, it is surprising that the direct role of NPs on neutrophil biology is poorly documented. Here, we investigated if ZnO NPs can alter neutrophil biology. We found that ZnO NPs increased the cell size, induced cell shape changes, activated phosphorylation events, enhanced cell spreading onto glass, but did not induce the generation of reactive oxygen species (ROS). Treatment of neutrophils with ZnO NPs markedly and significantly inhibited apoptosis and increased de novo protein synthesis, as demonstrated by gel electrophoresis of metabolically [(35)S]-labeled cells. Utilization of the protein synthesis inhibitor, cycloheximide, reversed such antiapoptotic effect. We conclude that ZnO NPs are activators of several human neutrophil functions and that they inhibit apoptosis by a de novo protein synthesis-dependent and ROS-independent mechanism. This is the first example that a NP acts on the neo-synthesis of polypeptides.
Laboratoire de recherche en inflammation et physiologie des granulocytes, Université du Québec, INRS-Institut Armand-Frappier, Laval, Quebec, Canada.
David M
DM
Goncalves
Laboratoire de recherche en inflammation et physiologie des granulocytes, Université du Québec, INRS-Institut Armand-Frappier, Laval, Quebec, Canada. Electronic address: denis.girard@iaf.inrs.ca.
D
D
Girard
D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D053758:Nanoparticles / Q000633:toxicity*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species; D015034:Zinc Oxide / Q000633:toxicity*
D011500:Protein Synthesis Inhibitors; D017382:Reactive Oxygen Species; D003513:Cycloheximide; D015034:Zinc Oxide
Apoptosis; Inflammation; Nanoparticle; Neutrophils; Protein synthesis; ZnO