title: Magnetite- and maghemite-induced different toxicity in murine alveolar macrophage cells.
abstract: The unique properties of nanoparticles and biological systems are important factors affecting the biological response following nanoparticle exposure. Iron oxide nanoparticles are classified mainly as magnetite (M-FeNPs) and maghemite (NM-FeNPs). In our previous study, NM-FeNPs induced autophagic cell death in RAW264.7, a murine peritoneal macrophage cell line, which has excellent lysosomal activity. In this study, we compared the toxicity of M-FeNPs and NM-FeNPs in MH-S, a murine alveolar macrophage cell line, which has relatively low lysosomal activity. At 24 h post-exposure, M-FeNPs decreased cell viability and ATP production, and elevated the levels of reactive oxygen species, nitric oxide, and pro-inflammatory cytokines to a higher extent than NM-FeNPs. Damage of mitochondria and the endoplasmic reticulum and the down-regulation of mitochondrial function and transcription-related genes were also higher in cells exposed to M-FeNPs than in cells exposed to NM-FeNPs (50 μg/ml). In addition, cells exposed to M-FeNPs (50 μg/ml) showed an increase in the number of autophagosome-like vacuoles, whereas cells exposed to NM-FeNPs formed large vacuoles in the cytosol. However, an autophagy-related molecular response was not induced by exposure to either FeNPs, unlike the results seen in our previous study with RAW264.7 cells. We suggest that M-FeNPs induced higher toxicity compared to NM-FeNPs in MH-S cells, and lysosomal activity plays an important role in determining cell death pathway.
authors: Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, Korea, pejtoxic@hanmail.net.
authors: Eun-Jung
authors: EJ
authors: Park
authors: Ha Nee
authors: HN
authors: Umh
authors: Dong-Hyuk
authors: DH
authors: Choi
authors: Myung Haing
authors: MH
authors: Cho
authors: Wookhee
authors: W
authors: Choi
authors: Sang-Wook
authors: SW
authors: Kim
authors: Younghun
authors: Y
authors: Kim
authors: Jae-Ho
authors: JH
authors: Kim
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005290:Ferric Compounds / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D058185:Magnetite Nanoparticles / Q000633:toxicity*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016207:Cytokines; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D017382:Reactive Oxygen Species; C000499:ferric oxide; D009569:Nitric Oxide; D000255:Adenosine Triphosphate