title: Genetic variation influences immune responses in sensitive rats following exposure to TiO2 nanoparticles.
abstract: This study examines the immunological responses in rats following inhalation to titanium dioxide nanoparticles (TiO2 NPs), in naïve rats and in rats with induced allergic airway disease. The responses of two different inbred rat strains were compared: the Dark Aguoti (DA), susceptible to chronic inflammatory disorders, and the Brown Norwegian (BN), susceptible to atopic allergic inflammation. Naïve rats were exposed to an aerosol of TiO2 NPs once daily for 10 days. Another subset of rats was sensitized to the allergen ovalbumin (OVA) in order to induce airway inflammation. These sensitized rats were exposed to TiO2 NPs before and during the allergen challenge. Naïve rats exposed to TiO2 NPs developed an increase of neutrophils and lymphocytes in both rat strains. Airway hyperreactivity and production of inflammatory mediators typical of a T helper 1 type immune response were significantly increased, only in DA rats. Sensitization of the rats induced a prominent OVA-specific-IgE and IgG response in the BN rat while DA rats only showed an increased IgG response. Sensitized rats of both strains developed airway eosinophilia following allergen challenge, which declined upon exposure to TiO2 NPs. The level of neutrophils and lymphocytes increased upon exposure to TiO2 NPs in the airways of DA rats but remained unchanged in the airways of BN rats. In conclusion, the responses to TiO2 NPs were strain-dependent, indicating that genetics play a role in both immune and airway reactivity. DA rats were found to be higher responder compared to BN rats, both when it comes to responses in naïve and sensitized rats. The impact of genetically determined factors influencing the inflammatory reactions pinpoints the complexity of assessing health risks associated with nanoparticle exposures.
authors.affiliation: Division of CBRN Defence and Security, Swedish Defence Research Agency, Umeå, Sweden; Department of Public Health and Clinical Medicine, Unit of Respiratory medicine, Umeå University, Umeå, Sweden. Electronic address: asa.gustafsson@foi.se.
authors.forename: Asa
authors.initials: A
authors.lastname: Gustafsson
authors.affiliation: Division of CBRN Defence and Security, Swedish Defence Research Agency, Umeå, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Jonasson
authors.affiliation: Department of Public Health and Clinical Medicine, Unit of Respiratory medicine, Umeå University, Umeå, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sandström
authors.affiliation: The Institute of Environmental Medicine, Unit of Work Environment Toxicology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johnny C
authors.initials: JC
authors.lastname: Lorentzen
authors.affiliation: Division of CBRN Defence and Security, Swedish Defence Research Agency, Umeå, Sweden; Department of Public Health and Clinical Medicine, Unit of Respiratory medicine, Umeå University, Umeå, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Bucht
mesh_terms: D000336:Aerosols; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000097:blood / Q000139:chemically induced* / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D014644:Genetic Variation; D005838:Genotype; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D018836:Inflammation Mediators / Q000378:metabolism; D019570:Inhalation Exposure / Q000009:adverse effects; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010047:Ovalbumin; D010641:Phenotype; D011014:Pneumonia / Q000097:blood / Q000139:chemically induced* / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D011914:Rats, Inbred BN; D012307:Risk Factors; D013045:Species Specificity; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D014025:Titanium / Q000633:toxicity*
chemical_list: D000336:Aerosols; D016207:Cytokines; D007074:Immunoglobulin G; D018836:Inflammation Mediators; C009495:titanium dioxide; D007073:Immunoglobulin E; D010047:Ovalbumin; D014025:Titanium
keywords: Aerosol inhalation; Asthma; Immune response; Inflammation; Ovalbumin; Titanium dioxide