title: Effects of subtoxic concentrations of TiO2 and ZnO nanoparticles on human lymphocytes, dendritic cells and exosome production.
abstract: Metal oxide nanoparticles are widely used in the paint and coating industry as well as in cosmetics, but the knowledge of their possible interactions with the immune system is very limited. Our aims were to investigate if commercially available TiO(2) and ZnO nanoparticles may affect different human immune cells and their production of exosomes, nano-sized vesicles that have a role in cell to cell communication. We found that the TiO(2) or ZnO nanoparticles at concentrations from 1 to 100μg/mL did not affect the viability of primary human peripheral blood mononuclear cells (PBMC). In contrast, monocyte-derived dendritic cells (MDDC) reacted with a dose dependent increase in cell death and caspase activity to ZnO but not to TiO(2) nanoparticles. Non-toxic exposure, 10μg/mL, to TiO(2) and ZnO nanoparticles did not significantly alter the phenotype of MDDC. Interestingly, ZnO but not TiO(2) nanoparticles induced a down regulation of FcγRIII (CD16) expression on NK-cells in the PBMC population, suggesting that subtoxic concentrations of ZnO nanoparticles might have an effect on FcγR-mediated immune responses. The phenotype and size of exosomes produced by PBMC or MDDC exposed to the nanoparticles were similar to that of exosomes harvested from control cultures. TiO(2) or ZnO nanoparticles could not be detected within or associated to exosomes as analyzed with TEM. We conclude that TiO(2) and ZnO nanoparticles differently affect immune cells and that evaluations of nanoparticles should be performed even at subtoxic concentrations on different primary human immune cells when investigating potential effects on immune functions.
authors: Translational Immunology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors: Britta
authors: B
authors: Andersson-Willman
authors: Ulf
authors: U
authors: Gehrmann
authors: Zekiye
authors: Z
authors: Cansu
authors: Tina
authors: T
authors: Buerki-Thurnherr
authors: Harald F
authors: HF
authors: Krug
authors: Susanne
authors: S
authors: Gabrielsson
authors: Annika
authors: A
authors: Scheynius
mesh_terms: D020170:Caspase 1 / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D055354:Exosomes / Q000187:drug effects / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D053758:Nanoparticles; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity*; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG; C009495:titanium dioxide; D014025:Titanium; D020170:Caspase 1; D015034:Zinc Oxide