Interaction between iron oxide nanoparticles (Fe3O4 NPs) and human neutrophils: Evidence that Fe3O4 NPs possess some pro-inflammatory activities

Abstract

Iron oxide nanoparticles (Fe3O4 NPs) are important for different medical applications. However, potential toxicity has been reported and several parameters must still be studied to reach highest therapeutic efficacy with minimal undesired effects. Inflammation is one of the most reported undesired effects of NP exposure in a variety of inflammatory models and conflicting data exist regarding whether Fe3O4 NPs possess pro- or anti-inflammatory activities. The aim of this study was to determine the direct effect of Fe3O4 NPs on the biology of neutrophil, a key player cell in inflammation. Freshly isolated human neutrophils were incubated in vitro with Fe3O4 NPs, and several functions have been studied. Using transmission electronic microscopy, Fe3O4 NPs were found to be ingested by neutrophils. These NPs do not induce a respiratory burst by themselves, but they increase the ability of neutrophils to adhere onto human endothelial cells as well as enhance phagocytosis. An antibody array approach revealed that Fe3O4 NPs induce the production of some cytokines, including the chemokine IL-8 (CXCL8), which was confirmed by ELISA. Fe3O4NPs were found to delay spontaneous neutrophil apoptosis regardless of sex of the donor. Using a pharmacological approach, we demonstrate that Fe3O4 NPs delay apoptosis by a de novo protein synthesis-dependent mechanism and via different cell signalling pathways. The data indicate that Fe3O4 NPs can alter the biology of human neutrophils and that they possess some pro-inflammatory effects, particularly based on their capacity to delay apoptosis and to induce the production of pro-inflammatory cytokines. Therefore, Fe3O4 NPs can regulate inflammation by targeting human neutrophil functions.