Silver nanoparticles (AgNP) are among the fastest growing categories of manufactured nanomaterials, and there is a need to investigate the risk for potential adverse effects of respiratory exposure in workers. The goal of the current study was to characterize susceptibility to lung bacterial infection following AgNP exposure in vivo. AgNP, 20 nm in diameter with a 0.3% wt polyvinylpovidone coating (NanoAmor, Inc.), were suspended in a physiological dispersion medium (DM) and sonicated. On day 0, rats were intratracheally (IT) instilled with 37.6 (Ag Low) or 449 (Ag High) microg of AgNP in DM or DM alone. On day 3, rats were inoculated IT with 5x105 Listeria monocytogenes (LM). Rats were euthanized on day 3 (pre-infection), and on days 4, 6, 8, and 10. Bronchoalveolar lavage (BAL) was performed on the right lung. The left lung was cultured to assess LM burden, and the lung-associated lymph nodes (LALN) were harvested. BAL cells and fluid were retained for analysis of injury, inflammation and oxidant production, and LALN lymphocytes were counted to assess immune response. On day 3 pre-infection, increased BAL albumin levels (lung injury) neutrophil influx (inflammation), LALN lymphocytes, and BAL cell oxidant production were measured in the Ag High group when compared to the Ag Low and DM groups. Following infection, LM lung burden increased significantly in the DM and Ag Low groups as compared to the Ag High group, peaking on day 6, with the highest burden in the DM group. LALN lymphocytes and BAL neutrophils, lymphocytes, and cellular oxidant production were elevated in the Ag High group on days 4 and 6 compared to DM and Ag Low groups. By day 8, LM lung burden, and BAL and LALN cell counts were similar for all groups. Induction of an early inflammatory response and oxidant burst in conjunction with increased lymphocyte proliferation in the lungs of the high dose AgNP group prior to infection enhanced the innate immune response and led to an increased clearance rate of bacteria from the lungs.
Toxicology; Nanotechnology; Laboratory-animals; Exposure-assessment; Exposure-levels; Dose-response; Silver-compounds; Respiratory-system-disorders; Pulmonary-system-disorders; Lung-disorders; Lung-irritants; In-vivo-study; Bacteria; Bacterial-cultures; Lung-burden; Lymph-nodes; Lymphocytes; Neutrophils; Immune-reaction; Oxidation; Lung-cells; Cellular-reactions
The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas