title: Carbon nanotubes activate store-operated calcium entry in human blood platelets.
abstract: Carbon nanotubes (CNTs) are known to potentiate arterial thrombosis in animal models, which raises serious safety issues concerning environmental or occupational exposure to CNTs and their use in various biomedical applications. We have shown previously that different CNTs, but not fullerene (nC60), induce the aggregation of human blood platelets. To date, however, a mechanism of potentially thrombogenic CNT-induced platelet activation has not been elucidated. Here we show that pristine multiwalled CNTs (MWCNTs) penetrate platelet plasma membrane without any discernible damage but interact with the dense tubular system (DTS) causing depletion of platelet intracellular Ca(2+) stores. This process is accompanied by the clustering of stromal interaction molecule 1 (STIM1) colocalized with Orai1, indicating the activation of store-operated Ca(2+) entry (SOCE). Our findings reveal the molecular mechanism of CNT-induced platelet activation which is critical in the evaluation of the biocompatibility of carbon nanomaterials with blood.
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20852-1448, USA.
authors.forename: Silvia H De Paoli
authors.initials: SH
authors.lastname: Lacerda
authors.forename: Jana
authors.initials: J
authors.lastname: Semberova
authors.forename: Karel
authors.initials: K
authors.lastname: Holada
authors.forename: Olga
authors.initials: O
authors.lastname: Simakova
authors.forename: Steven D
authors.initials: SD
authors.lastname: Hudson
authors.forename: Jan
authors.initials: J
authors.lastname: Simak
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D037742:Nanotubes, Carbon; D015539:Platelet Activation / Q000187:drug effects
chemical_list: D015220:Calcium Channels; D037742:Nanotubes, Carbon; D002118:Calcium