title: TiO2, CeO2 and ZnO nanoparticles and modulation of the degranulation process in human neutrophils.
abstract: Inflammation is frequently associated with nanoparticle (NP) exposures. Given that excessive polymorphonuclear neutrophil cell degranulation is a common feature of inflammatory disorders, and since these cells are key players in inflammation, we decided to test the hypothesis that NPs could act as modulators of degranulation in human neutrophils. TiO2, CeO2 and ZnO NPs slightly down-regulated cell surface expression of the granule marker CD35, but increased CD66b and CD63 expression, as assessed by flow cytometry. In addition, expression of myeloperoxidase, MMP-9 and albumin stored in azurophil, specific/gelatinase and secretrory granules, respectively, was significantly increased in the supernatants of NPs-induced neutrophils when compared to untreated cells. Moreover, NPs were more potent than the classical bacterial tripeptide N-formyl-methionine-leucine-phenylalanine (fMLP) agonist. Finally, TiO2 and CeO2 markedly increased the enzymatic activity of MMP-9 released into the supernatant, as assessed by gelatin zymography, while ZnO exerted only a modest effect. We conclude that NPs can differentially affect all steps involved during neutrophil degranulation, namely, cell surface expression of granule markers, liberation of proteins in the supernatants and enzymatic activity. These results are expected to be helpful to understand the toxicity of TiO2, CeO2 and ZnO.
authors.affiliation: Laboratoire de recherche en inflammation et physiologie des granulocytes, Université du Québec, INRS-Institut Armand-Frappier, Laval, QC, Canada.
authors.forename: Kim
authors.initials: K
authors.lastname: Babin
authors.forename: Francis
authors.initials: F
authors.lastname: Antoine
authors.forename: David Miguel
authors.initials: DM
authors.lastname: Goncalves
authors.forename: Denis
authors.initials: D
authors.lastname: Girard
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000418:Albumins / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002563:Cerium / Q000633:toxicity*; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000633:toxicity; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010316:Particle Size; D009195:Peroxidase / Q000378:metabolism; D058105:Polymerization; D014025:Titanium / Q000633:toxicity*; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D000418:Albumins; C009495:titanium dioxide; D002563:Cerium; D009240:N-Formylmethionine Leucyl-Phenylalanine; C030583:ceric oxide; D014025:Titanium; D009195:Peroxidase; D020780:Matrix Metalloproteinase 9; D015034:Zinc Oxide
keywords: Degranulation; Inflammation; Nanotoxicology; Neutrophils