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.
Highlights
Materials at the nanoscale often exhibit unique and beneficial functional properties which are not apparent in their larger counterparts
Exposure to Ag NMs had a significant impact on the metabolic activity of differentiated HL-60 cells (dHL-60) cells and primary neutrophils, with concentrations over 62.5 mg/mL resulting in complete cell death in both cell types (Figure 1(A)). dHL-60 metabolic activity was impacted by zinc oxide (ZnO) NMs and reduced to 35% at a concentration of 15.6 mg/mL
Despite the prominent role neutrophils play in NMinduced inflammation in rodents in vivo, it is surprising that only a limited number of studies have investigated neutrophil responses to NMs in vitro
Summary
Materials at the nanoscale often exhibit unique and beneficial functional properties which are not apparent in their larger counterparts. This has been exploited by various industrial and commercial sectors, and the manufacture of engineered nanomaterials (NMs) with tunable physicochemical characteristics has seen rapid growth in recent years. The novel, size-dependent properties of NMs raise concerns regarding their potential risk to human health and the environment. Evidence linking carbon particles found in air pollution with adverse health effects in humans demonstrates that nanomaterials emitted by anthropogenic activities have the potential to be toxic (Seaton et al 1995). There is an urgent need to devise testing strategies that allow for the rapid and reliable screening of NM safety
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