title: Characterizing the inhibitory action of zinc oxide nanoparticles on allergic-type mast cell activation.
abstract: The development of nanoparticles (NPs) for commercial products is undergoing a dramatic expansion. Many sunscreens and cosmetics now use zinc oxide (ZnO) or titania (TiO2) NPs, which are effective ultraviolet (UV) filters. Zinc oxide topical creams are also used in mild anti-inflammatory treatments. In this study we evaluated the effect of size and dispersion state of ZnO and TiO2 NPs, compared to "bulk" ZnO, on mast cell degranulation and viability. ZnO and TiO2 NPs were characterized using dynamic light scattering and disc centrifugation. Rat basophilic leukaemia (RBL-2H3) cells and primary mouse bone marrow-derived mast cells (BMMCs) were exposed to ZnO and TiO2 NPs of different sizes (25-200 nm) and surface coatings at concentrations from 1 to 200 μg/mL. The effect of NPs on immunoglobulin E (IgE)-dependent mast cell degranulation was assessed by measuring release of both β-hexosaminidase and histamine via colorimetric and ELISA assays. The intracellular level of Zn(2+) and Ca(2+) ions were measured using zinquin ethyl ester and Fluo-4 AM fluorescence probes, respectively. Cellular viability was determined using the soluble tetrazolium-based MTS colorimetric assay. Exposure of RBL-2H3 and primary mouse BMMC to ZnO NPs markedly inhibited both histamine and β-hexosaminidase release. This effect was both particle size and dispersion dependent. In contrast, TiO2 NPs did not inhibit the allergic response. These effects were independent of cytotoxicity, which was observed only at high concentrations of ZnO NPs, and was not observed for TiO2 NPs. The inhibitory effects of ZnO NPs on mast cells were inversely proportional to particle size and dispersion status, and thus these NPs may have greater potential than "bulk" zinc in the inhibition of allergic responses.
authors.affiliation: School of Medical Sciences, RMIT University, Melbourne, Australia; Department of Materials Engineering, Monash University, Melbourne, Australia. Electronic address: bryce.feltis@rmit.edu.au.
authors.forename: B N
authors.initials: BN
authors.lastname: Feltis
authors.affiliation: Faculty of Veterinary Medicine, Tripoli University, Tripoli, Libya.
authors.forename: A
authors.initials: A
authors.lastname: Elbaz
authors.affiliation: School of Medical Sciences, RMIT University, Melbourne, Australia.
authors.forename: P F A
authors.initials: PF
authors.lastname: Wright
authors.affiliation: Department of Pharmacology & Therapeutics, University of Melbourne, Melbourne, Australia.
authors.forename: G A
authors.initials: GA
authors.lastname: Mackay
authors.affiliation: Department of Materials Engineering, Monash University, Melbourne, Australia.
authors.forename: T W
authors.initials: TW
authors.lastname: Turney
authors.affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University, Townsville, Australia; School of Applied Sciences, RMIT University, Melbourne, Australia.
authors.forename: A L
authors.initials: AL
authors.lastname: Lopata
mesh_terms: D000818:Animals; D001491:Basophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006632:Histamine / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D061251:Primary Cell Culture; D051381:Rats; D014025:Titanium / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism; D015034:Zinc Oxide / Q000494:pharmacology*; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D002413:Cations, Divalent; C009495:titanium dioxide; D006632:Histamine; D014025:Titanium; D001619:beta-N-Acetylhexosaminidases; D015032:Zinc; D015034:Zinc Oxide; D002118:Calcium
keywords: BMMCs; Cytotoxicity; Histamine; RBL-2H3; TiO(2); ZnO; β-Hexosaminidase