Representative images of a, b) vehicle control and c–f) NiO nanoparticles (NPs) 4 weeks post-instillation. a) Normal alveolar structure consisting of thin.

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Representative images of a, b) vehicle control and c–f) NiO nanoparticles (NPs) 4 weeks post-instillation. a) Normal alveolar structure consisting of thin type I cells (black arrow). b) Compared with small macrophages in the vehicle control (black arrow), c... Representative images of a, b) vehicle control and c–f) NiO nanoparticles (NPs) 4 weeks post-instillation. a) Normal alveolar structure consisting of thin type I cells (black arrow). b) Compared with small macrophages in the vehicle control (black arrow), c) large foamy macrophages were found in the alveoli of NiO NP-treated lungs (black arrow); note that foamy macrophages contained numerous complex phospholipoprotein inclusions. c) Proteinaceous material was deposited in the alveoli (white arrow), and d) a higher-power view revealed these to be consistent with the large-aggregate form of surfactant (white arrow) and lamellar bodies (black arrows). e) Higher-power view of the electron-dense granules located in the rectangle inside the foamy macrophage in c), revealing them to be NiO NPs (black arrows). f) Low-power view to show proliferating and vacuolated type II epithelial cells in NiO NP-treated lungs (white arrows). Scale bars: a) 5 μm; b) 5 μm; c) 2 μm; d) 0.5 μm; e) 0.1 μm; f) 5 μm. W-S. Cho et al. Eur Respir J 2012;39:546-557 ©2012 by European Respiratory Society