Activation of human neutrophils by titanium dioxide (TiO2) nanoparticles.

This paper describes the in vitro effects of titanium dioxide (TiO(2)) nanoparticles (NPs) upon human neutrophils. Kinetic experiments revealed no cell necrosis after 24h of treatment with TiO(2) (0-100 microg/ml). In contrast, TiO(2)-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 TiO(2) 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 TiO(2) on two neutrophil functions requiring a longer exposure period between NPs and cells: apoptosis and cytokine production. Interestingly, at concentrations >or=20 microg/ml, TiO(2) inhibited neutrophil apoptosis in a concentration-dependent manner after 24h of treatment. Supernatants from TiO(2)-induced neutrophils were harvested after 24h and tested for the presence of 36 different analytes (cytokines, chemokines) using an antibody array assay. TiO(2) treatment increased production of 13 (36%) analytes, including IL-8, which exhibited the greatest increase ( approximately 16 x control cell levels). The increased production of IL-8 was confirmed by ELISA. We conclude that TiO(2) exerts important neutrophil agonistic properties in vitro.