title: Differential pro-inflammatory effects of metal oxide nanoparticles and their soluble ions in vitro and in vivo; zinc and copper nanoparticles, but not their ions, recruit eosinophils to the lungs.
abstract: Abstract   Nickel, zinc, and copper oxide nanoparticles (NiONP, ZnONP, and CuONP) and their aqueous extracts (AEs) were applied to A549 lung epithelial cells to determine the cytotoxicity, IL-8 production, and activation of transcription factors. Nanoparticles (NPs) and their AEs were also instilled into rat lungs to evaluate acute and chronic inflammatory effects. In vitro AEs had specific effects; for example NiOAE had no effect and ZnOAE affected all parameters measured. NPs themselves all had cytotoxic effects but only ZnONP and CuONP impacted pro-inflammatory endpoints. The inflammatory cells in the BAL were also different from AEs and NPs with ZnONP and CuONP recruiting eosinophils and neutrophils whilst ZnOAE and CuOAE elicited only mild neutrophilic inflammation that had resolved by four weeks. NiONP recruited neutrophils only whilst NiOAE did not cause any inflammation. Understanding differences in the toxic role of the ionic components of metal oxide NPs will contribute to full hazard identification and characterisation.
authors.affiliation: Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
authors.forename: Wan-Seob
authors.initials: WS
authors.lastname: Cho
authors.forename: Rodger
authors.initials: R
authors.lastname: Duffin
authors.forename: Craig A
authors.initials: CA
authors.lastname: Poland
authors.forename: Albert
authors.initials: A
authors.lastname: Duschl
authors.forename: Gertie Janneke
authors.initials: GJ
authors.lastname: Oostingh
authors.forename: William
authors.initials: W
authors.lastname: Macnee
authors.forename: Mark
authors.initials: M
authors.lastname: Bradley
authors.forename: Ian L
authors.initials: IL
authors.lastname: Megson
authors.forename: Ken
authors.initials: K
authors.lastname: Donaldson
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002417:Cattle; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003300:Copper / Q000633:toxicity; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007442:Intubation, Intratracheal; D007477:Ions; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053768:Metal Nanoparticles / Q000633:toxicity*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009532:Nickel / Q000633:toxicity; D010087:Oxides / Q000494:pharmacology*; D051381:Rats; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015034:Zinc Oxide / Q000633:toxicity
chemical_list: D016209:Interleukin-8; D007477:Ions; D010087:Oxides; D018808:Transcription Factor AP-1; D003300:Copper; D009532:Nickel; C028007:nickel monoxide; D015034:Zinc Oxide; C000520:cuprous oxide; C030973:cupric oxide