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Silver (Ag) is known as an antibacterial agent and there is a growing interest to use silver nanoparticles (AgNPs) in a variety of medical applications and other sectors. Some studies reported that one of the undesired effects of AgNPs is inflammation and that these NPs can alter the biology of neutrophils. Since it is commonly accepted that the more NPs are small, the more toxic they are the aim of this study was to determine the impact of ultra-small silver nanoparticles of 2 nm (AgNP 2 ) on the biology of neutrophils, key player cells in inflammation. We report that AgNP 2 are potent neutrophil activators as they rapidly induce actin polymerization and dismantling the actin network. Although AgNP 2 are not necrotic for neutrophils and do not induce ROS production, kinetic studies reveal that AgNP 2 are rapid inducer of apoptosis. Pyknosis (mainly 1-2 large nuclear dots) was observed after only 1h of treatment followed by karyorrhexis (several small dots) and by a complete nuclear dissolution leading to anuclear neutrophils after 6h. These observations are not associated with the release of silver ions since treatment of neutrophils with 1-50 μg/ml AgNO 3 (as a source of Ag + ) did not induce any apparent changes. AgNP 2 induce p38 and Erk-1/2 mitogen-activated protein kinase (MAPK) and although karyorrhexis was markedly reversed by MAPK inhibitors, the cell nuclei remain with a pyknotic-like phenotype but do not return to the characteristic polylobed nucleus. Using the murine air pouch model of inflammation AgNP 2 were found to induce a neutrophil influx. Our data indicate that AgNP 2 are potent neutrophil activators targeting the actin cytoskeleton and the mechanism involved for inducing apoptosis is rapid, complex, and partially includes MAPK pathways. Therefore, the ultra-small AgNP 2 are more potent than larger ones for inducing apoptosis and they can transitorily attract neutrophils in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Iron oxide nanoparticles (Fe 3 O 4 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 Fe 3 O 4 NPs possess pro- or anti-inflammatory activities. The aim of this study was to determine the direct effect of Fe 3 O 4 NPs on the biology of neutrophil, a key player cell in inflammation. Freshly isolated human neutrophils were incubated in vitro with Fe 3 O 4 NPs, and several functions have been studied. Using transmission electronic microscopy, Fe 3 O 4 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 Fe 3 O 4 NPs induce the production of some cytokines, including the chemokine IL-8 (CXCL8), which was confirmed by ELISA. Fe 3 O 4 NPs were found to delay spontaneous neutrophil apoptosis regardless of sex of the donor. Using a pharmacological approach, we demonstrate that Fe 3 O 4 NPs delay apoptosis by a de novo protein synthesis-dependent mechanism and via different cell signalling pathways. The data indicate that Fe 3 O 4 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, Fe 3 O 4 NPs can regulate inflammation by targeting human neutrophil functions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)