Nanoparticles induce platelet activation in vitro through stimulation of canonical signalling pathways

Nanomaterials are attracting growing interest for their potential use in several applications as nanomedicine; therefore, the analysis of their potential toxic effects on various cellular models, including circulating blood cells, is mandatory. This study aimed to investigate the effect of three unrelated nanomaterials, namely nanoscale silica, multiwalled carbon nanotubes, and carbon black, on platelet activation and aggregation. We found that these nanomaterials stimulate some of the typical biochemical pathways involved in canonical platelet activation, such as the stimulation of phospholipase C and Rap1b, resulting in the integrin αIIbβ3-mediated platelet aggregation, through a mechanism largely dependent on the release of the extracellular second messengers ADP and thromboxane A2. Importantly, we found that doses of nanoparticles unable to trigger appreciable responses can synergize with subthreshold amounts of physiological agonists to mediate platelet aggregation, indicating that even small amounts of nanomaterials in the bloodstream might contribute to the development of thrombosis.From the Clinical EditorIn this study, nanosized particles of three virtually unrelated materials (silica, multi-walled carbon nanotubes and carbon black) were investigated regarding their effects on platelet activation and aggregation. All were found to stimulate some of the typical biochemical pathways involved in canonical platelet activation, and were found to have synergistic effects with physiologic platelet activator agonists.

Graphical AbstractExposure of platelets to Hi-Sil T700TM, multiwalled carbon nanotubes (MWCNT), or carbon black promotes stimulation of canonical signalling pathways that involve the activation of phospholipase C (PLC), protein kinase C (PKC), and the small GTPase Rap1. Platelet activation is supported by the release of the extracellular second messengers ADP and thromboxane A2 (TxA2), that cooperate with nanomaterials to promote integrin αIIbβ3-dependent platelet aggregation.Figure optionsDownload high-quality image (82 K)Download as PowerPoint slide