Cytotoxicity of silica nanoparticles through exocytosis of von Willebrand factor and necrotic cell death in primary human endothelial cells

TY - JOUR

T1 - Cytotoxicity of silica nanoparticles through exocytosis of von Willebrand factor and necrotic cell death in primary human endothelial cells

AU - Bauer, Alexander T

AU - Strozyk, Elwira A

AU - Gorzelanny, Christian

AU - Westerhausen, Christoph

AU - Desch, Anna

AU - Schneider, Matthias F

AU - Schneider, Stefan W

N1 - Copyright © 2011 Elsevier Ltd. All rights reserved.

PY - 2011/11

Y1 - 2011/11

N2 - Nanoparticle-induced endothelial cell (EC) dysfunction, due to the induction of inflammation and/or the activation of the coagulation system, is associated with pulmonary and ischemic cardiovascular diseases. Although it is contigent on several mechanisms, involving formation of reactive oxygen species and inflammatory cytokines such as interleukin (IL)-6 and 8, the involvement of the coagulation system is not well understood. The results of toxicity assays using the tetrazolium reduction (MTT) and lactate dehydrogenase (LDH) release showed that silica NP-induced cytotoxicity depends on the size and the dose of applied NP. Moreover, propidium iodide (PI) stainings and caspase 3/7 assays identified increased necrosis in ECs. Exposing human umbilical vein endothelial cells (HUVECs) to SiO(2) NP with diameters of 304 nm and 310 nm led to significant increase of Weibel-Palade body (WPB) exocytosis, associated with the release of von Willebrand factor (VWF) and the formation of ultralarge fibers (ULVWF). High resolution microscopy techniques revealed that internalization and perinuclear localization of perylene-labeled NP with a size of 310 nm affect not only viability, but also cell migration and proliferation. In conclusion, our data indicate that NP-induced activation and dysfunction of ECs is reflected by release of VWF and necrotic cell death.

AB - Nanoparticle-induced endothelial cell (EC) dysfunction, due to the induction of inflammation and/or the activation of the coagulation system, is associated with pulmonary and ischemic cardiovascular diseases. Although it is contigent on several mechanisms, involving formation of reactive oxygen species and inflammatory cytokines such as interleukin (IL)-6 and 8, the involvement of the coagulation system is not well understood. The results of toxicity assays using the tetrazolium reduction (MTT) and lactate dehydrogenase (LDH) release showed that silica NP-induced cytotoxicity depends on the size and the dose of applied NP. Moreover, propidium iodide (PI) stainings and caspase 3/7 assays identified increased necrosis in ECs. Exposing human umbilical vein endothelial cells (HUVECs) to SiO(2) NP with diameters of 304 nm and 310 nm led to significant increase of Weibel-Palade body (WPB) exocytosis, associated with the release of von Willebrand factor (VWF) and the formation of ultralarge fibers (ULVWF). High resolution microscopy techniques revealed that internalization and perinuclear localization of perylene-labeled NP with a size of 310 nm affect not only viability, but also cell migration and proliferation. In conclusion, our data indicate that NP-induced activation and dysfunction of ECs is reflected by release of VWF and necrotic cell death.

KW - Cell Death

KW - Cells, Cultured

KW - Dose-Response Relationship, Drug

KW - Endothelium, Vascular

KW - Exocytosis

KW - Fluorescent Antibody Technique

KW - Humans

KW - Microscopy, Atomic Force

KW - Nanoparticles

KW - Necrosis

KW - Particle Size

KW - Silicon Dioxide

KW - Wound Healing

KW - von Willebrand Factor

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.biomaterials.2011.07.078

DO - 10.1016/j.biomaterials.2011.07.078

M3 - SCORING: Journal article

C2 - 21840590

VL - 32

SP - 8385

EP - 8393

JO - BIOMATERIALS

JF - BIOMATERIALS

SN - 0142-9612

IS - 33

ER -