Nanoparticles in the lungs of old mice: Pulmonary inflammation and oxidative stress without procoagulant effects

Pulmonary exposure to nanoparticles (NPs) has been shown to induce pulmonary as well as cardiovascular toxicity. These effects might be enhanced in elderly subjects as a result of a compromised immunity and/or declined organ functions. To study the adverse in vivo effects of NPs in amodel for the elderly, we exposed 18-month-old C75Bl/6mice tomulti-walled carbon nanotubes (MWCNTs) or ZnO NPs by intratracheal instillation once a week during 5 consecutiveweeks. Pulmonary and hemostatic toxicitywas determined 24 h (T1) and 8weeks (T2) after the last administration. Both NP types significantly increased the pulmonary macrophages at both time points. The MWCNTs and ZnO NPs also induced a pulmonary influx of neutrophils, whichwas even larger at T2 compared to T1. All NPs induced only amodest increase of pulmonary IL-1 beta, IL-6 and KC levels. Both types of NPs also increased blood neutrophils. Red blood cells were not significantly affected. Both NPs significantly increased coagulation factor VIII levels at both time points. Histological analysis revealed the presence of MWCNTs in the alveolar macrophages up to 8 weeks after the last administration and the ZnO NPs induced a pronounced alveolar inflammation.