Nanomaterials : respiratory and immunological effects following inhalation of engineered nanoparticles

Sammanfattning: 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.