Inflammatory response of lung macrophages and epithelial cells after exposure to redox active nanoparticles: effect of solubility and antioxidant treatment.

The effects of an exposure to three mass-produced metal oxide nanoparticles-similar in size and specific surface area but different in redox activity and solubility-were studied in rat alveolar macrophages (MAC) and epithelial cells (AEC). We hypothesized that the cell response depends on the particle redox activity and solubility determining the amount of reactive oxygen species formation (ROS) and subsequent inflammatory response. MAC and AEC were exposed to different amounts of Mn3O4 (soluble, redox-active), CeO2 (insoluble, redox-active), and TiO2 (insoluble, redox-inert) up to 24 h. Viability and inflammatory response were monitored with and without coincubation of a free-radical scavenger (trolox). In MAC elevated ROS levels, decreased metabolic activity and attenuated inflammatory mediator secretion were observed in response to Mn3O4. Addition of trolox partially resolved these changes. In AEC, decreased metabolic activity and an attenuated inflammatory mediator secretion were found in response to CeO2 exposure without increased production of ROS, thus not sensitive to trolox administration. Interestingly, highly redox-active soluble particles did not provoke an inflammatory response. The data reveal that target and effector cells of the lung react in different ways to particle exposure making a prediction of the response depending on redox activity and intracellular solubility difficult.