Titanium dioxide nanoparticles induce human eosinophil adhesion onto endothelial EA.hy926 cells via activation of phosphoinositide 3-kinase/Akt cell signalling pathway.

The use of nanoparticles (NPs) for developing new therapeutic strategies in a variety of diseases is gaining increasing attention. However, NPs could possess undesired effects, including pro-inflammatory activities. Despite the fact that several studies reported that NPs may induce or exacerbate eosinophilic inflammation in vivo in rodents, the information regarding the direct interaction between NPs and human eosinophils is lacking. In the present study, we test the possibility that NPs could alter the capacity of human eosinophils to adhere onto a cellular substratum. Using a panel of NPs, we found that several were able to increase the adhesion of human eosinophil onto endothelial EA.hy926 cells. Among them, TiO2 NPs were the most potent and we therefore pursue this study with these NPs. TiO2 NPs were found to increase the adhesion of eosinophils in a concentration dependent fashion. TiO2 NPs did not alter the cell surface expression of a panel of cellular adhesion molecules, but CD29. Indeed, a weak to moderate, but significant, decrease of CD29 was observed after 30min but returned to normal levels after 90min. TiO2 NPs were found to activate Akt, one important target of phosphoinositide 3-kinase (PI3K). However, despite the fact that cells were fully responsive to the cytokine GM-CSF activating both Akt and Erk-1/2, TiO2 NPs did not activate Erk-1/2. Using a pharmacological approach with the PI3K/Akt inhibitor, wortmannin, the ability of TiO2 NPs to activate Akt was drastically inhibited and, further, their capacity to increase adhesion of eosinophils was reversed. This study provides insights into the effects of NPs on the biology of human eosinophils indicating that as other agents, NPs, namely TiO2 NPs, can induce intracellular events associated with a cellular function, adhesion.

WITHDRAWN: Titanium dioxide nanoparticles induce human eosinophil adhesion onto endothelial EA.hy926 cells via activation of phosphoinositide 3-kinase/Akt cell signalling pathway.

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Activation of human AML14.3D10 eosinophils by nanoparticles: Modulatory activity on apoptosis and cytokine production.

Eosinophilic inflammation is frequently observed in response to nanoparticle (NP) exposure in airway rodent models of allergies where the number of eosinophils is increased in lungs. Despite this, it is surprising that the potential cytotoxic effect of NP, as well as their direct role on eosinophils is poorly documented. The present study investigated how different NP can alter the biology of the human eosinophilic cell line AML14.3D10. It was found that among NP forms of CeO2, ZnO, TiO2, and nanosilver of 20 nm (AgNP20) or 70 nm (AgNP70) diameters, only ZnO and AgNP20 induced apoptosis. Caspases-7 and -9 were not activated by the tested NP while caspase-3 was activated by AgNP20 only. However, both ZnO and AgNP20 induced cytoskeletal breakdown as evidenced by the cleavage of lamin B1. Using an ELISArray approach for the simultaneous detection of several analytes (cytokines/chemokines), it was found that only ZnO and AgNP20 increased the production of different analytes including the potent pro-inflammatory CXCL8 (IL-8) chemokine. From the data here, we conclude that toxic effects of some NP could be observed in human eosinophil-like cells and that this could be related, at least partially, by induction of apoptosis and production of cytokines and chemokines involved in inflammation. The results of this study also indicate that distinct NP do not activate similarly human eosinophils, since ZnO and AgNP20 induce apoptosis and cytokine production while others such as TiO2, CeO2, and AgNP70 do not.