Abstract

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 [35S]-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.

Highlights

  • Nanomaterials are increasingly produced and the use of engineered nanoparticles (NPs) in a variety of sectors, including biomedical sciences, pharmaceutical industry, electronics, cosmetics, etc., is getting more and more common because the physicochemical properties of their small 1– 100 nm size differ from standard bulk materials

  • The results of this study demonstrate that zinc oxide (ZnO) are human neutrophil activators, as evidenced by the capacity of these NPs to induce cell shape changes, tyrosine phosphorylation events and cell spreading

  • The results demonstrating that ZnO induced tyrosine phosphorylation events indicate that, at least, NPs react with cell membrane to activate some signaling events

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Summary

Introduction

Nanomaterials are increasingly produced and the use of engineered nanoparticles (NPs) in a variety of sectors, including biomedical sciences, pharmaceutical industry, electronics, cosmetics, etc., is getting more and more common because the physicochemical properties of their small 1– 100 nm size differ from standard bulk materials. Besides having great anti-microbial properties, ZnO NPs are widely used in a variety of compounds, including cosmetics, sunscreens and toothpastes, to name a few (Heng et al, 2011 and Vandebriel and De Jong, 2012). Despite the widespread use of ZnO NPs, its safety for humans is unknown and the intracellular regulatory mechanisms involved in ZnO NPs-induced cytotoxicity reported in a variety of cells are unclear (Heng et al, 2011, Sahu et al, 2013, Vandebriel and De Jong, 2012 and Wilhelmi et al, 2013). Since the cytotoxicity and inflammatory properties of ZnO NPs appear to be cell type-dependent (Heng et al, 2011, Sahu et al, 2013, Vandebriel and De Jong, 2012 and Wilhelmi et al, 2013), the need to investigate how PMNs respond to these NPs is important. The aim of this study was to determine how ZnO NPs alter the biology of PMNs

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