Activation of human neutrophils by titanium dioxide (TiO2) nanoparticles

This paper describes the in vitro effects of titanium dioxide (TiO2) nanoparticles (NPs) upon human neutrophils. Kinetic experiments revealed no cell necrosis after 24 h of treatment with TiO2 (0–100 μg/ml). In contrast, TiO2-induced change in cellular morphology in a concentration-dependent manner in neutrophils over time, indicating its potential to activate these cells. To further support this, we demonstrated that TiO2 markedly and rapidly induced tyrosine phosphorylation events, including phosphorylation of two key enzymes, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases-1/2 (Erk-1/2). We also determined the effects of TiO2 on two neutrophil functions requiring a longer exposure period between NPs and cells: apoptosis and cytokine production. Interestingly, at concentrations ⩾20 μg/ml, TiO2 inhibited neutrophil apoptosis in a concentration-dependent manner after 24 h of treatment. Supernatants from TiO2-induced neutrophils were harvested after 24 h and tested for the presence of 36 different analytes (cytokines, chemokines) using an antibody array assay. TiO2 treatment increased production of 13 (36%) analytes, including IL-8, which exhibited the greatest increase (∼16 × control cell levels). The increased production of IL-8 was confirmed by ELISA. We conclude that TiO2 exerts important neutrophil agonistic properties in vitro.