title: Differential cellular responses in healthy mice and in mice with established airway inflammation when exposed to hematite nanoparticles.
abstract: The aim of this study was to investigate the inflammatory and immunological responses in airways and lung-draining lymph nodes (LDLNs), following lung exposure to iron oxide (hematite) nanoparticles (NPs). The responses to the hematite NPs were evaluated in both healthy non-sensitized mice, and in sensitized mice with an established allergic airway disease. The mice were exposed intratracheally to either hematite NPs or to vehicle (PBS) and the cellular responses were evaluated on days 1, 2, and 7, post-exposure. Exposure to hematite NPs increased the numbers of neutrophils, eosinophils, and lymphocytes in the airways of non-sensitized mice on days 1 and 2 post-exposure; at these time points the number of lymphocytes was also elevated in the LDLNs. In contrast, exposing sensitized mice to hematite NPs induced a rapid and unspecific cellular reduction in the alveolar space on day 1 post-exposure; a similar decrease of lymphocytes was also observed in the LDLN. The results indicate that cells in the airways and in the LDLN of individuals with established airway inflammation undergo cell death when exposed to hematite NPs. A possible explanation for this toxic response is the extensive generation of reactive oxygen species (ROS) in the pro-oxidative environment of inflamed airways. This study demonstrates how sensitized and non-sensitized mice respond differently to hematite NP exposure, and it highlights the importance of including individuals with respiratory disorders when evaluating health effects of inhaled nanomaterials.
authors.affiliation: Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden; Dept of Public Health and Clinical Medicine, Umeå University, Sweden. Electronic address: asa.gustafsson@foi.se.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Gustafsson
authors.affiliation: Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden; Dept of Organismal Biology, Uppsala University, SE-751 Uppsala, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Bergström
authors.affiliation: Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden.
authors.forename: Lina
authors.initials: L
authors.lastname: Ågren
authors.affiliation: Dept of Engineering Sciences, The Ångström Laboratory, Uppsala University, SE-751 Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Österlund
authors.affiliation: Dept of Public Health and Clinical Medicine, Umeå University, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sandström
authors.affiliation: Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden; Dept of Public Health and Clinical Medicine, Umeå University, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Bucht
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D016923:Cell Death / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D005290:Ferric Compounds / Q000633:toxicity*; D019570:Inhalation Exposure / Q000009:adverse effects*; D007700:Kinetics; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin; D018384:Oxidative Stress / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D016207:Cytokines; D005290:Ferric Compounds; D017382:Reactive Oxygen Species; C000499:ferric oxide; D010047:Ovalbumin
keywords: Hematite; Inflammation; Iron oxide; Nanoparticles; Reactive oxygen species; α-Fe(2)O(3)