Neutrophil activation by nanomaterials in vitro: comparing strengths and limitations of primary human cells with those of an immortalized (HL-60) cell line

Rachel Verdon, Suzanne L. Gillies, David M. Brown, Theodore Henry, Lang Tran, Charles R. Tyler, Adriano G. Rossi, Vicki Stone, Helinor J. Johnston

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
18 Downloads (Pure)

Abstract

Assessment of nanomaterial (NM) induced inflammatory responses has largely relied on rodent testing via measurement of leukocyte accumulation in target organs. Despite observations that NMs activate neutrophil driven inflammatory responses in vivo, a limited number of studies have investigated neutrophil responses to NMs in vitro. We compared responses between the human neutrophil-like HL-60 cell line and human primary neutrophils following exposure to silver (Ag), zinc oxide (ZnO), copper oxide (CuO) and titanium dioxide (TiO2) NMs. NM cytotoxicity and neutrophil activation were assessed by measuring cellular metabolic activity, cytokine production, respiratory burst, and release of neutrophil extracellular traps. We observed a similar pattern of response between HL-60 cells and primary neutrophils, however we report that some neutrophil functions are compromised in the cell line. Ag NMs were consistently observed to stimulate neutrophil activation, with CuO NMs inducing similar though weaker responses. TiO2 NMs did not induce a neutrophil response in either cell type. Interestingly, ZnO NMs readily induced activation of HL-60 cells but did not appear to activate primary cells. Our findings are relevant to the development of a tiered testing strategy for NM hazard assessment which promotes the use of non-rodent models. Whilst we acknowledge that HL-60 cells may not be a perfect substitute for primary cells and require further investigation regarding their ability to predict neutrophil activation, we recommend their use for initial screening of NM-induced inflammation. Primary human neutrophils can then be used for more focused assessments of neutrophil activation before progressing to in vivo models where necessary.

Original languageEnglish
JournalNanotoxicology
Early online date4 Dec 2020
DOIs
Publication statusE-pub ahead of print - 4 Dec 2020

Keywords

  • inflammation
  • in vitro
  • nanomaterial
  • nanotoxicology
  • Neutrophil

ASJC Scopus subject areas

  • Biomedical Engineering
  • Toxicology

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