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

Elina M. Rossi, Lea Pylkkänen, Antti J. Koivisto, Minnamari Vippola, Keld A. Jensen, Mirella Miettinen, Kristiina Sirola, Heli Nykäsenoja, Piia Karisola, Tuula Stjernvall, Esa Vanhala, Mirja Kiilunen, Pertti Pasanen, Maija Mäkinen, Kaarle Hämeri, Jorma Joutsensaari, Timo Tuomi, Jorma Jokiniemi, Henrik Wolff, Kai Savolainen & 2 others Sampsa Matikainen, Harri Alenius

Research output: Contribution to journalArticleScientificpeer-review

120 Citations (Scopus)

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 (TiO2) 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 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 nanosized SiO2 did not induce significant inflammation. Pulmonary neutrophilia was accompanied by increased expression of tumor necrosis factor-alpha (TNF-α) 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-α 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.
Original languageEnglish
Pages (from-to)422-433
JournalToxicological Sciences
Volume113
Issue number2
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

Fingerprint

Silicon Dioxide
Nanoparticles
Macrophages
Chemokine CXCL1
Lung
Neutrophils
Fibroblasts
Tumor Necrosis Factor-alpha
Coatings
Nanotechnology
Alveolar Macrophages
Interleukin-8
Chemokines
Particle Size
Risk assessment
Toxicology
Inhalation
Pneumonia
Industry
Gases

Keywords

  • engineered nanoparticles
  • inflammation
  • inhalation
  • Titanium dioxide

Cite this

Rossi, E. M., Pylkkänen, L., Koivisto, A. J., Vippola, M., Jensen, K. A., Miettinen, M., ... Alenius, H. (2010). Airway exposure to silica-coated TiO2 nanoparticles induces pulmonary neutrophilia in mice. Toxicological Sciences, 113(2), 422-433. https://doi.org/10.1093/toxsci/kfp254
Rossi, Elina M. ; Pylkkänen, Lea ; Koivisto, Antti J. ; Vippola, Minnamari ; Jensen, Keld A. ; Miettinen, Mirella ; Sirola, Kristiina ; Nykäsenoja, Heli ; Karisola, Piia ; Stjernvall, Tuula ; Vanhala, Esa ; Kiilunen, Mirja ; Pasanen, Pertti ; Mäkinen, Maija ; Hämeri, Kaarle ; Joutsensaari, Jorma ; Tuomi, Timo ; Jokiniemi, Jorma ; Wolff, Henrik ; Savolainen, Kai ; Matikainen, Sampsa ; Alenius, Harri. / Airway exposure to silica-coated TiO2 nanoparticles induces pulmonary neutrophilia in mice. In: Toxicological Sciences. 2010 ; Vol. 113, No. 2. pp. 422-433.
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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 (TiO2) 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 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 nanosized SiO2 did not induce significant inflammation. Pulmonary neutrophilia was accompanied by increased expression of tumor necrosis factor-alpha (TNF-α) 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-α 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.",
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Rossi, EM, Pylkkänen, L, Koivisto, AJ, Vippola, M, Jensen, KA, Miettinen, M, Sirola, K, Nykäsenoja, H, Karisola, P, Stjernvall, T, Vanhala, E, Kiilunen, M, Pasanen, P, Mäkinen, M, Hämeri, K, Joutsensaari, J, Tuomi, T, Jokiniemi, J, Wolff, H, Savolainen, K, Matikainen, S & Alenius, H 2010, 'Airway exposure to silica-coated TiO2 nanoparticles induces pulmonary neutrophilia in mice', Toxicological Sciences, vol. 113, no. 2, pp. 422-433. https://doi.org/10.1093/toxsci/kfp254

Airway exposure to silica-coated TiO2 nanoparticles induces pulmonary neutrophilia in mice. / Rossi, Elina M.; Pylkkänen, Lea; Koivisto, Antti J.; Vippola, Minnamari; Jensen, Keld A.; Miettinen, Mirella; Sirola, Kristiina; Nykäsenoja, Heli; Karisola, Piia; Stjernvall, Tuula; Vanhala, Esa; Kiilunen, Mirja; Pasanen, Pertti; Mäkinen, Maija; Hämeri, Kaarle; Joutsensaari, Jorma; Tuomi, Timo; Jokiniemi, Jorma; Wolff, Henrik; Savolainen, Kai; Matikainen, Sampsa; Alenius, Harri (Corresponding Author).

In: Toxicological Sciences, Vol. 113, No. 2, 2010, p. 422-433.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Airway exposure to silica-coated TiO2 nanoparticles induces pulmonary neutrophilia in mice

AU - Rossi, Elina M.

AU - Pylkkänen, Lea

AU - Koivisto, Antti J.

AU - Vippola, Minnamari

AU - Jensen, Keld A.

AU - Miettinen, Mirella

AU - Sirola, Kristiina

AU - Nykäsenoja, Heli

AU - Karisola, Piia

AU - Stjernvall, Tuula

AU - Vanhala, Esa

AU - Kiilunen, Mirja

AU - Pasanen, Pertti

AU - Mäkinen, Maija

AU - Hämeri, Kaarle

AU - Joutsensaari, Jorma

AU - Tuomi, Timo

AU - Jokiniemi, Jorma

AU - Wolff, Henrik

AU - Savolainen, Kai

AU - Matikainen, Sampsa

AU - Alenius, Harri

PY - 2010

Y1 - 2010

N2 - 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 (TiO2) 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 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 nanosized SiO2 did not induce significant inflammation. Pulmonary neutrophilia was accompanied by increased expression of tumor necrosis factor-alpha (TNF-α) 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-α 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.

AB - 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 (TiO2) 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 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 nanosized SiO2 did not induce significant inflammation. Pulmonary neutrophilia was accompanied by increased expression of tumor necrosis factor-alpha (TNF-α) 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-α 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.

KW - engineered nanoparticles

KW - inflammation

KW - inhalation

KW - Titanium dioxide

U2 - 10.1093/toxsci/kfp254

DO - 10.1093/toxsci/kfp254

M3 - Article

VL - 113

SP - 422

EP - 433

JO - Toxicological Sciences

JF - Toxicological Sciences

SN - 1096-6080

IS - 2

ER -

Rossi EM, Pylkkänen L, Koivisto AJ, Vippola M, Jensen KA, Miettinen M et al. Airway exposure to silica-coated TiO2 nanoparticles induces pulmonary neutrophilia in mice. Toxicological Sciences. 2010;113(2):422-433. https://doi.org/10.1093/toxsci/kfp254