1. Mechanism of neutrophil activation and toxicity elicited by engineered nanomaterials
- Author
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Adriano G. Rossi, Elizabeth Dyrynda, Birgit K Gaiser, Helinor Jane Johnston, Euan R. Brown, Matthew Euston, David M. Brown, Calum T. Robb, Nilesh Kanase, and Vicki Stone
- Subjects
Silver ,Cell Survival ,HL60 ,Inorganic chemistry ,HL-60 Cells ,Toxicology ,Neutrophil Activation ,chemistry.chemical_compound ,Soot ,Superoxides ,Humans ,Cytotoxicity ,Titanium ,chemistry.chemical_classification ,Reactive oxygen species ,Nanotubes, Carbon ,Superoxide ,General Medicine ,Nanostructures ,chemistry ,Toxicity ,Biophysics ,Cytokines ,Calcium ,Trolox ,Zinc Oxide ,Cell activation ,Intracellular - Abstract
The effects of nanomaterials (NMs) on biological systems, especially their ability to stimulate inflammatory responses requires urgent investigation. We evaluated the response of the human differentiated HL60 neutrophil-like cell line to NMs. It was hypothesised that NM physico-chemical characteristics would influence cell responsiveness by altering intracellular Ca2+ concentration [Ca2+]i and reactive oxygen species production. Cells were exposed (1.95–125 μg/ml, 24 h) to silver (Ag), zinc oxide (ZnO), titanium dioxide (TiO2), multi-walled carbon nanotubes (MWCNTs) or ultrafine carbon black (ufCB) and cytotoxicity assessed (alamar blue assay). Relatively low (TiO2, MWCNTs, ufCB) or high (Ag, ZnO) cytotoxicity NMs were identified. Sub-lethal impacts of NMs on cell function were investigated for selected NMs only, namely TiO2, Ag and ufCB. Only Ag stimulated cell activation. Within minutes, Ag stimulated an increase in [Ca2+]i (in Fura-2 loaded cells), and a prominent inward ion current (assessed by electrophysiology). Within 2–4 h, Ag increased superoxide anion release and stimulated cytokine production (MCP-1, IL-8) that was diminished by Ca2+ inhibitors or trolox. Light microscopy demonstrated that cells had an activated phenotype. In conclusion NM toxicity was ranked; Ag > ufCB > TiO2, and the battery of tests used provided insight into the mechanism of action of NM toxicity to guide future testing strategies.
- Published
- 2015