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ToxSci Advance Access published online on October 29, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp254
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© The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Airway exposure to silica coated TiO2 nanoparticles induces pulmonary neutrophilia in mice

Rossi EM*, Pylkkänen L*, Koivisto AJ{dagger}, Vippola M{dagger},{ddagger}, Jensen KA§, Miettinen M, Sirola K*, Nykäsenoja H*, Karisola P*, Stjernvall T||, Vanhala E|||, Kiilunen M||||, Pasanen P#, Mäkinen M#, Hämeri K{dagger},**, Joutsensaari J{dagger}{dagger}, Tuomi T|||, Jokiniemi J,a, Wolff H||, Savolainen K{dagger}, Matikainen S* and Alenius H*

* Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health, 00250 Helsinki, Finland {dagger} New Technologies and Risks, Finnish Institute of Occupational Health, 00250 Helsinki, Finland {ddagger} Department of Materials Science, Tampere University of Technology, 33720 Tampere, Finland § National Research Centre for the Working Environment, 2100 Copenhagen, Denmark Fine Particle and Aerosol Technology Laboratory, Department of Environmental Science, University of Kuopio, 70211 Kuopio, Finland || Biological Mechanisms and Prevention of Work-Related Diseases/Immunopathology, Finnish Institute of Occupational Health, 00250 Helsinki, Finland ||| Aerosols, Dusts and Metals, Finnish Institute of Occupational Health, 00250 Helsinki, Finland |||| Risk Assessment and Biomonitoring, Finnish Institute of Occupational Health, 00250 Helsinki, Finland # Department of Environmental Science, University of Kuopio, 70211 Kuopio, Finland ** Department of Physics, University of Helsinki, 00014 Helsinki, Finland {dagger}{dagger} Department of Physics, University of Kuopio, 70211 Kuopio, Finland a Fine Particles, VTT Technical Research Centre of Finland, 02044 Espoo, Finland

Corresponding author: Harri Alenius, Harri.Alenius{at}ttl.fi, Topeliuksenkatu 41b, FIN-00250 Helsinki, Finland

Received August 13, 2009; revision received October 14, 2009; accepted October 15, 2009


  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 TiO2 particles are used in industry we explored their inflammatory potential using mouse and cell models. BALB/c mice were exposed by inhalation for either 2 hours, 2 hours on four consecutive days or 2 hours on four consecutive days for four weeks to several commercial TiO2 nanoparticles, SiO2 nanoparticles and to nanosized TiO2 generated in a gas-to-particle conversion process at 10 mg/m3. In addition, effects of in vitro exposure of human macrophages and fibroblasts (MRC-9) to the different particles were assessed. SiO2-coated rutile TiO2 nanoparticles (cnTiO2) was the only sample tested that elicited clear-cut pulmonary neutrophilia. Uncoated rutile and anatase as well as nanosize SiO2 did not induce significant inflammation. Pulmonary neutrophilia was accompanied by increased expression of TNF-{alpha} and neutrophil attracting chemokine CXCL1 in the lung tissue. TiO2 particles accumulated almost exclusively in the alveolar macrophages. In vitro exposure of murine and human macrophages to cnTiO2 elicited significant induction of TNF-{alpha} and neutrophil attracting chemokines. Stimulation of human fibroblasts with cnTiO2-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.

Key Words: Engineered nanoparticles; titanium dioxide; inhalation; inflammation.

Elina Rossi, Elina.Rossi{at}ttl.fi; Lea Pylkkänen, Lea.Pylkkanen{at}ttl.fi; Antti Joonas Koivisto, Joonas.Koivisto{at}ttl.fi; Minnamari Vippola, Minnamari.Vippola{at}ttl.fi; Keld Alstrup Jensen, kaj{at}nrcwe.dk; Mirella Miettinen, Mirella.Miettinen{at}uku.fi; Kristiina Sirola, Kristiina.Sirola{at}ttl.fi; Heli Nykäsenoja, hnykasen{at}cc.hut.fi; Piia Karisola, Piia.Karisola{at}ttl.fi; Tuula Stjernvall, Tuula.Stjernvall{at}ttl.fi; Esa Vanhala, Esa.Vanhala{at}ttl.fi; Mirja Kiilunen, Mirja.Kiilunen{at}ttl.fi; Pertti Pasanen, Pertti.Pasanen{at}uku.fi; Maija Mäkinen, Maija.Makinen{at}uku.fi; Kaarle Hämeri, Kaarle.Hameri{at}ttl.fi; Jorma Joutsensaari, Jorma.Joutsensaari{at}uku.fi; Timo Tuomi, Timo.Tuomi{at}ttl.fi; Jorma Jokiniemi, Jorma.Jokiniemi{at}vtt.fi; Henrik Wolff, Henrik.Wolff{at}ttl.fi; Kai Savolainen, Kai.Savolainen{at}ttl.fi; Sampsa Matikainen, Sampsa.Matikainen{at}ttl.fi


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