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Mechanistic Differences in Cell Death Responses to Metal‐Based Engineered Nanomaterials in Kupffer Cells and Hepatocytes
Author(s) -
Wang Xiang,
Chang Chong Hyun,
Jiang Jinhong,
Liu Xiangsheng,
Li Jiulong,
Liu Qi,
Liao YuPei,
Li Linjiang,
Nel André E.,
Xia Tian
Publication year - 2020
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.202000528
Subject(s) - pyroptosis , programmed cell death , inflammasome , apoptosis , nanotoxicology , microbiology and biotechnology , reactive oxygen species , chemistry , caspase , biophysics , materials science , nanotechnology , biochemistry , biology , nanoparticle , receptor
The mononuclear phagocyte system in the liver is a frequent target for nanoparticles (NPs). A toxicological profiling of metal‐based NPs is performed in Kupffer cell (KC) and hepatocyte cell lines. Sixteen NPs are provided by the Nanomaterial Health Implications Research Consortium of the National Institute of Environmental Health Sciences to study the toxicological effects in KUP5 (KC) and Hepa 1–6 cells. Five NPs (Ag, CuO, ZnO, SiO 2 , and V 2 O 5 ) exhibit cytotoxicity in both cell types, while SiO 2 and V 2 O 5 induce IL‐1β production in KC. Ag, CuO, and ZnO induced caspase 3 generated apoptosis in both cell types is accompanied by ion shedding and generation of mitochondrial reactive oxygen species (ROS) in both cell types. However, the cell death response to SiO 2 in KC differs by inducing pyroptosis as a result of potassium efflux, caspase 1 activation, NLRP3 inflammasome assembly, IL‐1β release, and cleavage of gasdermin‐D. This releases pore‐performing peptide fragments responsible for pyroptotic cell swelling. Interestingly, although V 2 O 5 induces IL‐1β release and delays caspase 1 activation by vanadium ion interference in membrane Na + /K + adenosine triphosphate (ATP)ase activity, the major cell death mechanism in KC (and Hepa 1–6) is caspase 3 mediated apoptosis. These findings improve the understanding of the mechanisms of metal‐based engineered nanomaterial (ENM) toxicity in liver cells toward comprehensive safety evaluation.