RRC ID 67173
Author Mirshafiee V, Sun B, Chang CH, Liao YP, Jiang W, Jiang J, Liu X, Wang X, Xia T, Nel AE.
Title Toxicological Profiling of Metal Oxide Nanoparticles in Liver Context Reveals Pyroptosis in Kupffer Cells and Macrophages versus Apoptosis in Hepatocytes.
Journal ACS Nano
Abstract The liver and the mononuclear phagocyte system are a frequent target for engineered nanomaterials, either as a result of particle uptake and spread from primary exposure sites or systemic administration of therapeutic and imaging nanoparticles. In this study, we performed a comparative analysis of the toxicological impact of 29 metal oxide nanoparticles (NPs), some commonly used in consumer products, in transformed or primary Kupffer cells (KCs) and hepatocytes. We not only observed differences between KCs and hepatocytes, but also differences in the toxicological profiles of transition-metal oxides (TMOs, e. g., Co3O4) versus rare-earth oxide (REO) NPs ( e. g., Gd2O3). While pro-oxidative TMOs induced the activation of caspases 3 and 7, resulting in apoptotic cell death in both cell types, REOs induced lysosomal damage, NLRP3 inflammasome activation, caspase 1 activation, and pyroptosis in KCs. Pyroptosis was accompanied by cell swelling, membrane blebbing, IL-1β release, and increased membrane permeability, which could be reversed by knockdown of the pore forming protein, gasdermin D. Though similar features were not seen in hepatocytes, the investigation of the cytotoxic effects of REO NPs could also be seen to affect macrophage cell lines such as J774A.1 and RAW 264.7 cells as well as bone marrow-derived macrophages. These phagocytic cell types also demonstrated features of pyroptosis and increased IL-1β production. Collectively, these findings demonstrate important mechanistic considerations that can be used for safety evaluation of metal oxides, including commercial products that are developed from these materials.
Volume 12(4)
Pages 3836-3852
Published 2018-4-24
DOI 10.1021/acsnano.8b01086
PMID 29543433
PMC PMC5946698
MeSH Animals Apoptosis / drug effects* Cell Line Cell Survival / drug effects Female Hepatocytes / drug effects Hepatocytes / metabolism Humans Kupffer Cells / drug effects Kupffer Cells / metabolism Liver / drug effects* Liver / metabolism Macrophages / drug effects Macrophages / metabolism Mice Mice, Inbred C57BL Nanoparticles / chemistry* Oxides / chemistry Oxides / pharmacology* RAW 264.7 Cells Transition Elements / chemistry Transition Elements / pharmacology*
IF 14.588
Human and Animal Cells KUP5(RCB4627)