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Inflammation and fate of quantum dots following pulmonary treatment of rats.

Roberts-JR; Mercer-RR; Young-S; Porter-DW; Castranova-V; Antonini-JM
Toxicologist 2007 Mar; 96(1):230
Inhalation of nanoparticles may affect the respiratory, cardiovascular, and central nervous systems. The mechanism by which nanoparticles translocate from the airspaces into the bloodstream is unknown. The goal was to investigate the fate and inflammatory effects of fluorescent quantum dots (30-50 nm; coated with carboxyl terminal groups) after pulmonary exposure. To monitor phagocytosis of quantum dots by non-primed and primed alveolar macrophages (AM) in vitro, AM were collected by bronchoalveolar lavage (BAL) from untreated rats or rats that had been treated by pulmonary inoculation with L. monocytogenes. AM were incubated for 2 hr with 0 (control), 2.5, or 25 g/ml of quantum dots and mounted for laser scanning confocal microscopy (LSCM) or analyzed by flow cytometry to quantify phagocytosis. For in vivo studies, male Sprague-Dawley rats were intratracheally instilled with saline or quantum dots on day 0 at a dose of 12.5 g/rat. At 2 hr postinstillation, and on days 1, 3, and 5, the left lungs were cryopreserved and sectioned for LSCM. BAL was performed on right lungs, and indicators of lung damage were measured. Collected lavage cells were differentiated to assess inflammation. Recovered AM also were mounted onto slides and analyzed by LSCM to assess uptake of the quantum dots in vivo. A concentration-dependent increase in the phagocytosis of the quantum dots by AM in vitro was observed. A greater number of quantum dots were phagocytized by the primed AM. At 2 hr post-instillation, quantum dots were located in the AM and airspaces, as well as on the epithelial surfaces, in the alveolar region. By 24 hr, most of the quantum dots had been phagocytized by AM, and localized areas of quantum particles were observed in interstitial areas of lung parenchyma. Lung injury and inflammation were found to be elevated in the BAL of animals treated with quantum dots on 1, 3 and 5 days postexposure compared to saline controls. Due to their high intensity fluorescent signal, quantum dots appear to be appropriate for studying the pulmonary deposition and fate of nanoparticles.
Biodynamics; Animal-studies; Lung-disorders; Lung-irritants; Lung-cells; Pulmonary-disorders; Pulmonary-function-tests; Pulmonary-system-disorders; Cell-damage; Respiratory-infections; Respiratory-irritants; Respiratory-function-tests; In-vivo-studies; Particle-aerodynamics; Particulates; Inhalation-studies; Cardiovascular-system-disorders; Cardiopulmonary-system-disorders; Central-nervous-system-disorders; Nanotechnology
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The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina