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Research article - Peer-reviewed, 2018

Contact (kallikrein/kinin) system activation in whole human blood induced by low concentrations of alpha-Fe2O3 nanoparticles

Ekdahl, Kristina N.; Davoodpour, Padideh; Ekstrand-Hammarstrom, Barbro; Fromell, Karin; Hamad, Osama A.; Hong, Jaan; Bucht, Anders; Mohlin, Camilla; Seisenbaeva, Gulaim A.; Kessler, Vadim G.; Nilsson, Bo

Abstract

Iron-oxide nanoparticles (NPs) generated by environmental events are likely to represent health problems. alpha-Fe2O3 NPs were synthesized, characterized and tested in a model for toxicity utilizing human whole blood without added anticoagulant. MALDI-TOF of the corona was performed and activation markers for plasma cascade systems (complement, contact and coagulation systems), platelet consumption and release of growth factors, MPO, and chemokine/cytokines from blood cells were analyzed. The coronas formed on the pristine alpha-Fe2O3 NPs contained contact system proteins and they induced massive activation of the contact (kinin/kallikrein) system, as well as thrombin generation, platelet activation, and release of two pro-angiogeneic growth factors: platelet-derived growth factor and vascular endothelial growth factor, whereas complement activation was unaffected. The alpha-Fe2O3 NPs exhibited a noticeable toxicity, with kinin/kallikrein activation, which may be associated with hypotension and long-term angiogenesis in vivo, with implications for cancer, arteriosclerosis and pulmonary disease. (c) 2017 Elsevier Inc. All rights reserved.

Keywords

alpha-Fe2O3 NPs; Contact/kallikrein system; Innate immunity

Published in

Nanomedicine: Nanotechnology, Biology and Medicine
2018, Volume: 14, number: 3, pages: 735-744
Publisher: ELSEVIER SCIENCE BV