Effects of gadolinium oxide nanoparticles on the oxidative burst from human neutrophil granulocytes

Abstract

We have previously shown that gadolinium oxide (Gd(2)O(3)) nanoparticles are promising candidates to be used as contrast agents in magnetic resonance (MR) imaging applications. In this study, these nanoparticles were investigated in a cellular system, as possible probes for visualization and targeting intended for bioimaging applications. We evaluated the impact of the presence of Gd(2)O(3) nanoparticles on the production of reactive oxygen species (ROS) from human neutrophils, by means of luminol-dependent chemiluminescence. Three sets of Gd(2)O(3) nanoparticles were studied, i.e. as synthesized, dialyzed and both PEG-functionalized and dialyzed Gd(2)O(3) nanoparticles. In addition, neutrophil morphology was evaluated by fluorescent staining of the actin cytoskeleton and fluorescence microscopy. We show that surface modification of these nanoparticles with polyethylene glycol (PEG) is essential in order to increase their biocompatibility. We observed that the as synthesized nanoparticles markedly decreased the ROS production from neutrophils challenged with prey (opsonized yeast particles) compared to controls without nanoparticles. After functionalization and dialysis, more moderate inhibitory effects were observed at a corresponding concentration of gadolinium. At lower gadolinium concentration the response was similar to that of the control cells. We suggest that the diethylene glycol (DEG) present in the as synthesized nanoparticle preparation is responsible for the inhibitory effects on the neutrophil oxidative burst. Indeed, in the present study we also show that even a low concentration of DEG, 0.3%, severely inhibits neutrophil function. In summary, the low cellular response upon PEG-functionalized Gd(2)O(3) nanoparticle exposure indicates that these nanoparticles are promising candidates for MR-imaging purposes.

Intracellular Signal Modulation by Nanomaterials

“…Under physiological conditions this enzyme complex is latent in phagocytic cells. However, nanomaterials can activate the inflammatory cells inducing a respiratory burst in the absence of bacteria (Abrikossova et al, 2012, Tulinska et al, 2013). NADPH oxidase is abundant in “professional” phagocytes but this protein is also present in non inflammatory cells where it contributes to cell signaling.…”

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

“…Nevertheless, the safety of these nanoparticles, as well as their effects in host defense system, remains unestablished. Particularly, direct activation of polymorphonuclear neutrophil cells (PMNs), key player cells in inflammation, by different AgNPs is poorly documented, despite the fact that accumulating data indicate that PMN biology could be altered by different kinds of NPs [5][6][7][8][9][10][11].…”

Silver nanoparticles of 70 nm and 20 nm affect differently the biology of human neutrophils

“…Despite this, the literature dealing with the direct effects of NP on PMN is not well documented, even if our group (Babin et al 2013;Goncalves and Girard 2014;Goncalves et al 2010;Poirier et al 2014) and others (Abrikossova et al 2012;Bartneck et al 2010;Chekanov et al 2013;Couto et al 2014;Moeller et al 2012;Papatheofanis and Barmada 1991) reported that different kinds of NP can activate human PMN, leading to distinct modulatory activities on functional responses including reactive oxygen species (ROS) production, cytokine formation, apoptosis and degranulation. Among these studies, it was previously reported that silver NP (AgNP) with a diameter of 20 nm (AgNP 20 ) induced human neutrophil apoptosis and inhibited de novo protein synthesis (Poirier et al 2014).…”