title: Airway exposure to silica-coated TiO2 nanoparticles induces pulmonary neutrophilia in mice.
abstract: The importance of nanotechnologies and engineered nanoparticles has grown rapidly. It is therefore crucial to acquire up-to-date knowledge of the possible harmful health effects of these materials. Since a multitude of different types of nanosized titanium dioxide (TiO(2)) particles are used in industry, we explored their inflammatory potential using mouse and cell models. BALB/c mice were exposed by inhalation for 2 h, 2 h on 4 consecutive days, or 2 h on 4 consecutive days for 4 weeks to several commercial TiO(2) nanoparticles, SiO(2) nanoparticles, and to nanosized TiO(2) generated in a gas-to-particle conversion process at 10 mg/m(3). In addition, effects of in vitro exposure of human macrophages and fibroblasts (MRC-9) to the different particles were assessed. SiO(2)-coated rutile TiO(2) nanoparticles (cnTiO(2)) was the only sample tested that elicited clear-cut pulmonary neutrophilia. Uncoated rutile and anatase as well as nanosized SiO(2) did not induce significant inflammation. Pulmonary neutrophilia was accompanied by increased expression of tumor necrosis factor-alpha (TNF-alpha) and neutrophil-attracting chemokine CXCL1 in the lung tissue. TiO(2) particles accumulated almost exclusively in the alveolar macrophages. In vitro exposure of murine and human macrophages to cnTiO(2) elicited significant induction of TNF-alpha and neutrophil-attracting chemokines. Stimulation of human fibroblasts with cnTiO(2)-activated macrophage supernatant induced high expression of neutrophil-attracting chemokines, CXCL1 and CXCL8. Interestingly, the level of lung inflammation could not be explained by the surface area of the particles, their primary or agglomerate particle size, or radical formation capacity but is rather explained by the surface coating. Our findings emphasize that it is vitally important to take into account in the risk assessment that alterations of nanoparticles, e.g., by surface coating, may drastically change their toxicological potential.
authors.affiliation: Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Elina M
authors.initials: EM
authors.lastname: Rossi
authors.forename: Lea
authors.initials: L
authors.lastname: Pylkkänen
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Koivisto
authors.forename: Minnamari
authors.initials: M
authors.lastname: Vippola
authors.forename: Keld A
authors.initials: KA
authors.lastname: Jensen
authors.forename: Mirella
authors.initials: M
authors.lastname: Miettinen
authors.forename: Kristiina
authors.initials: K
authors.lastname: Sirola
authors.forename: Heli
authors.initials: H
authors.lastname: Nykäsenoja
authors.forename: Piia
authors.initials: P
authors.lastname: Karisola
authors.forename: Tuula
authors.initials: T
authors.lastname: Stjernvall
authors.forename: Esa
authors.initials: E
authors.lastname: Vanhala
authors.forename: Mirja
authors.initials: M
authors.lastname: Kiilunen
authors.forename: Pertti
authors.initials: P
authors.lastname: Pasanen
authors.forename: Maija
authors.initials: M
authors.lastname: Mäkinen
authors.forename: Kaarle
authors.initials: K
authors.lastname: Hämeri
authors.forename: Jorma
authors.initials: J
authors.lastname: Joutsensaari
authors.forename: Timo
authors.initials: T
authors.lastname: Tuomi
authors.forename: Jorma
authors.initials: J
authors.lastname: Jokiniemi
authors.forename: Henrik
authors.initials: H
authors.lastname: Wolff
authors.forename: Kai
authors.initials: K
authors.lastname: Savolainen
authors.forename: Sampsa
authors.initials: S
authors.lastname: Matikainen
authors.forename: Harri
authors.initials: H
authors.lastname: Alenius
mesh_terms: D000818:Animals; D019743:Chemokines, CXC / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D019570:Inhalation Exposure / Q000032:analysis*; D007964:Leukocytosis / Q000139:chemically induced* / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000633:toxicity*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology; D012822:Silicon Dioxide / Q000633:toxicity*; D014025:Titanium / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019743:Chemokines, CXC; D014409:Tumor Necrosis Factor-alpha; C009495:titanium dioxide; D012822:Silicon Dioxide; D014025:Titanium