Mice with established airway inflammation exert differential cellular responses to inhaled hematite nanoparticles than healthy mice
(English)Manuscript (preprint) (Other academic)
The aim of this study was to investigate the inflammatory and immunological responses in the airways and the lung-draining lymph nodes, following lung exposure to hematite nanoparticles (NPs). The responses to hematite NPs were evaluated in both non-sensitized healthy mice, and allergen-sensitized mice, in which the latter represent a group of sensitive individuals with allergic airway disease. This allergic airway disease was induced by sensitization and aerosol challenge to a respiratory allergen resulting in an established eosinophilic and lymphocytic airway inflammation at the time of NP exposure. The mice received either hematite NPs or vehicle (PBS) intratracheally and the cellular responses were evaluated on day 1, 2, and 7, following exposure.
Intratracheal instillation of hematite NPs induced an increase of neutrophils, eosinophils, and lymphocytes in the airways of non-sensitized mice on day 1 and 2 following exposure. At these time-points the lymphocytes in the lymph nodes were also increased. In contrast, exposure to hematite NPs in sensitized mice induced a rapid and unspecific cellular reduction in the alveolar space on the first day after exposure. A similar decrease of lymphocytes was also observed in the mediastinal lymph nodes draining the airways. The study did not indicate a reduction of inflammatory cells in the lung tissue or a translocation of cells from alveolar space to lung tissue. Although, mucociliary cellular clearance could be a possible explanation, our finding of cellular decrease also in lung draining lymph nodes point at cell death as the most likely cause to this unspecific cellular reduction.
The results indicate that cells in the airways and lymph nodes of individuals with established airway inflammation undergo cell death when exposed to iron oxide NPs. A possible reason to the toxic response is extensive generation of reactive oxygen species (ROS) in the pro-oxidative environment of inflamed airways, which is further catalyzed by Fe ions released by the hematite NPs, or by generation of ROS at the surface of the NPs. Such cell toxic response was not detected in healthy non-sensitized individuals. This study clearly demonstrates the different response of sensitized and non-sensitized mice, and highlights the importance of including individuals with respiratory disorders, such as allergic asthma, when evaluating health effects of inhaled nanomaterials.
Ironoxide, nanoparticles, asthma, allergy, lung, lymph node, lymphocytes, macrophages
Respiratory Medicine and Allergy Pharmacology and Toxicology
Research subject Toxicology; Occupational and Environmental Medicine; Lung Medicine; Immunology; nanoparticles; nanotoxicology
IdentifiersURN: urn:nbn:se:umu:diva-95969OAI: oai:DiVA.org:umu-95969DiVA: diva2:762067
FunderFormasForte, Swedish Research Council for Health, Working Life and Welfare
Forskningsfinansiär: Umeå center for environmental research, Swedish Minestry of Defence2014-11-102014-11-102014-11-14Bibliographically approved