Indium oxide nanoparticles induce lung intercellular toxicity between bronchial epithelial cells and macrophages

Concerns have been raised over the safety and health of industrial workers exposed to indium oxide nanoparticles (IO-NPs) when working. IO-NPs were previously shown in vitro and in vivo to be cytotoxic, but the mechanism of pathogenesis was unclear. In this study, the effects of IO-NPs on lung cells associated with respiratory and immune barriers and the toxic effects of intercellular cascades were studied. Here IO-NPs had acute toxicity to Wistar rats over a time course (5 days post-intratracheal instillation). Following treatment epithelial cells (16HBE) or macrophages (RAW264.7) with IO-NPs or IO fine particles (IO-FPs), the damage of 16HBE cells caused by IO-NPs was serious, mainly in the mitochondrial and rough endoplasmic reticulum. The lactate dehydrogenase level also showed that cytotoxicity in vitro was more serious for IO-NPs compared with IO-FPs. The level of In3+(examined by inductively coupled plasma mass spectrometry) in 16HBE cells was 10 times higher than that in RAW cells. In3+, releasing from IO-NPs absorbed by 16HBE cells, could not only significantly inhibit the phagocytosis and migration of macrophages (P< .0001), but also stimulate RAW cells to secrete high levels of inflammatory cytokines. IO-NPs can directly damage pulmonary epithelial cells. The In(3+)released by epithelial cells affect the phagocytosis and migration of macrophages, which may be a new point for the decrease in the clearance of alveolar surfactants and the development of IO-related pulmonary alveolar proteinosis.