Mechanism of neutrophil activation and toxicity elicited by engineered nanomaterials

Helinor Jane Johnston*, David McAllister Brown, Nilesh Kanase, Matthew Euston, Birgit Katja Gaiser, Calum Turnbull Robb, Elizabeth Dyrynda, Adriano G. Rossi, Euan R Brown, Vicki Stone

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


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 Ca<sup>2+</sup> concentration [Ca<sup>2+</sup>]<inf>i</inf> and reactive oxygen species production.Cells were exposed (1.95-125μg/ml, 24h) to silver (Ag), zinc oxide (ZnO), titanium dioxide (TiO<inf>2</inf>), multi-walled carbon nanotubes (MWCNTs) or ultrafine carbon black (ufCB) and cytotoxicity assessed (alamar blue assay). Relatively low (TiO<inf>2</inf>, 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 TiO<inf>2</inf>, Ag and ufCB. Only Ag stimulated cell activation. Within minutes, Ag stimulated an increase in [Ca<sup>2+</sup>]<inf>i</inf> (in Fura-2 loaded cells), and a prominent inward ion current (assessed by electrophysiology). Within 2-4h, Ag increased superoxide anion release and stimulated cytokine production (MCP-1, IL-8) that was diminished by Ca<sup>2+</sup> inhibitors or trolox. Light microscopy demonstrated that cells had an activated phenotype.In conclusion NM toxicity was ranked; Ag>ufCB>TiO<inf>2</inf>, and the battery of tests used provided insight into the mechanism of action of NM toxicity to guide future testing strategies.

Original languageEnglish
Pages (from-to)1172-1184
Number of pages13
JournalToxicology in Vitro
Issue number5
Early online date8 May 2015
Publication statusPublished - Aug 2015


  • Ca<sup>2+</sup>
  • Mechanism
  • Nanomaterial
  • Neutrophil
  • Toxicity

ASJC Scopus subject areas

  • General Agricultural and Biological Sciences
  • General Chemistry
  • General Materials Science
  • General Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)


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