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Inhalation exposure of nano-scaled titanium dioxide (TiO2) particles alters the inflammatory responses in asthmatic mice
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
2013 (English)In: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 25, no 4, 179-191 p.Article in journal (Refereed) Published
Abstract [en]

Context: Titanium dioxide (TiO2) nanoparticles (NPs) are regarded as relatively non-toxic in concentrations occurring in occupational environments. Nevertheless, it is conceivable that adverse health effects may develop in sensitive populations such as individuals with respiratory diseases.

Objective: We investigated whether single or repeated exposure to TiO2 could aggravate inflammatory responses in naive mice and mice with ovalbumin (OVA)-induced airway inflammation.

Methods: Exposure to aerosolized TiO2 was performed during OVA sensitization, before, or during the OVA challenge period. The effects on respiratory physiology, inflammatory cells in bronchoalveolar lavage (BAL) and inflammatory mediators in BAL and serum were assessed 24 h after the last OVA challenge or TiO2 exposure.

Results: A single exposure of TiO2 had a marked effect on responses in peripheral airways and increasing infiltration of neutrophils in airways of naive animals. Marked aggravation of airway responses was also observed in animals with allergic disease provided that the single dose TiO2 was given before allergen challenge. Repeated exposures to TiO2 during sensitization diminished the OVA-induced airway eosinophilia and airway hyperresponsiveness but concomitant exposure to TiO2 during the OVA challenge period resulted in neutrophilic airway inflammation and a decline in general health condition as indicated by the loss of body weight.

Conclusion: We conclude that inhalation of TiO2 may aggravate respiratory diseases and that the adverse health effects are highly dependent on dose and timing of exposure. Our data imply that inhalation of NPs may increase the risk for individuals with allergic airway disease to develop symptoms of severe asthma.

Place, publisher, year, edition, pages
Informa Healthcare, 2013. Vol. 25, no 4, 179-191 p.
Keyword [en]
Asthma, inflammation, nanomaterial, respiratory mechanics, titanium dioxide
National Category
Respiratory Medicine and Allergy Pharmacology and Toxicology
Research subject
Occupational and Environmental Medicine; Immunology; Lung Medicine; nanoparticles; nanotoxicology
Identifiers
URN: urn:nbn:se:umu:diva-71103DOI: 10.3109/08958378.2013.770939ISI: 000317459800001OAI: oai:DiVA.org:umu-71103DiVA: diva2:627403
Funder
FormasForte, Swedish Research Council for Health, Working Life and Welfare
Note

Forskningsfinansiär: Swedish Ministry of Defence

Available from: 2013-06-11 Created: 2013-05-20 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Nanomaterials: respiratory and immunological effects following inhalation of engineered nanoparticles
Open this publication in new window or tab >>Nanomaterials: respiratory and immunological effects following inhalation of engineered nanoparticles
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background Nanotechnology is an important and promising field that can lead to improved environment and human health and contribute to a better social and economic development. Materials in nanoscale have unique physiochemical properties which allow for completely new technical applications. Enlarged surface area and properties due to quantum physics are among the properties that distinguish the nanoscale. Nano safety has evolved as a discipline to evaluate the adverse health effects from engineered nanomaterials (ENMs). The prevalence of allergic diseases is increasing in the society. An additional issue is the influence of inherited factors on the health responses to ENMs. The aim of this thesis was to investigate the respiratory, inflammatory, and immunological effects following inhalation of ENMs; both sensitive and genetically susceptible individuals were used. Sensitive individuals refer to individuals with pre-existing respiratory diseases, such as allergic asthma, and genetically susceptible individuals refer to individuals prone to autoimmune and allergic diseases.

Methods In vivo models of mice and rats were used. In study I the inflammatory and immune responses following exposure to titanium dioxide nanoparticles (TiO2 NPs) were investigated. The effect of when the TiO2 NP exposure occurs during the development of allergic airway inflammation was investigated in study II, with regards to respiratory, inflammatory, and immune responses. In study III, the influence of the genetics on the respiratory, inflammatory, and immune responses, following TiO2 NP exposure to naïve and sensitive rats was evaluated. In study IV, the inflammatory and immune responses of naïve mice and mice with an allergic airway inflammation were studied in lung fluid and lymph nodes draining the airways following inhalation to hematite NPs (α-Fe2O2).

Results Exposure to TiO2 NPs induced a long-lasting lymphocytic response in the airways, indicating a persistent immune stimulation. The dose and timing of TiO2 NP exposure affected the airway response in mice with allergic airway disease. When the mice were exposed to particles and an allergen during the same period, a decline in general health was observed. By comparing different inbred rat strains it was demonstrated that genetically determined factors influence the immune and respiratory responses to TiO2 NP exposure in both naïve and sensitive individuals. Exposure to hematite NPs resulted in different cellular responses: naïve mice had increased numbers of cells while mice with allergic airway inflammation had decreased cell numbers in BALF. Analogous cell responses were also observed in the lung draining lymph nodes.

Conclusion Altogether, this thesis emphasises the complexity of assessing health risks associated with nanoparticle exposure and the importance of including sensitive populations when evaluating adverse health effects of ENMs.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2014. 78 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1686
Keyword
nanoparticles, nanomaterials, inhalation, lung, metalloxides
National Category
Respiratory Medicine and Allergy
Research subject
Immunology; Toxicology; Lung Medicine; Occupational and Environmental Medicine; nanoparticles; nanotoxicology
Identifiers
urn:nbn:se:umu:diva-95724 (URN)978-91-7601-168-3 (ISBN)
Public defence
2014-12-05, Hörsal 135, Allmänmedicin, byggnad 9B, Norrlands universitetssjukhus, Umeå, 13:00 (Swedish)
Opponent
Supervisors
Funder
FormasForte, Swedish Research Council for Health, Working Life and Welfare
Note

Forskningsfinansiär: Umeå Center for Environmental Research, and by the Swedish Ministry of Defence

Available from: 2014-11-14 Created: 2014-11-04 Last updated: 2014-11-14Bibliographically approved

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