title: Cytotoxicity of silica nanoparticles through exocytosis of von Willebrand factor and necrotic cell death in primary human endothelial cells.
abstract: 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.
authors.affiliation: Department of Dermatology, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Bauer
authors.forename: Elwira A
authors.initials: EA
authors.lastname: Strozyk
authors.forename: Christian
authors.initials: C
authors.lastname: Gorzelanny
authors.forename: Christoph
authors.initials: C
authors.lastname: Westerhausen
authors.forename: Anna
authors.initials: A
authors.lastname: Desch
authors.forename: Matthias F
authors.initials: MF
authors.lastname: Schneider
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Schneider
mesh_terms: D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D006801:Humans; D018625:Microscopy, Atomic Force; D053758:Nanoparticles; D009336:Necrosis; D010316:Particle Size; D012822:Silicon Dioxide; D014945:Wound Healing; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor; D012822:Silicon Dioxide