Mechanistic Differences in Cell Death Responses to Metal-Based Engineered Nanomaterials in Kupffer Cells and Hepatocytes
Xiang Wang
Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA, 90095 USA
California NanoSystems Institute, University of California, Los Angeles, CA, 90095 USA
Search for more papers by this authorChong Hyun Chang
California NanoSystems Institute, University of California, Los Angeles, CA, 90095 USA
Search for more papers by this authorJinhong Jiang
California NanoSystems Institute, University of California, Los Angeles, CA, 90095 USA
Search for more papers by this authorXiangsheng Liu
Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA, 90095 USA
Search for more papers by this authorJiulong Li
Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA, 90095 USA
Search for more papers by this authorQi Liu
Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA, 90095 USA
Search for more papers by this authorYu-Pei Liao
Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA, 90095 USA
Search for more papers by this authorLinjiang Li
California NanoSystems Institute, University of California, Los Angeles, CA, 90095 USA
Search for more papers by this authorCorresponding Author
André E. Nel
Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA, 90095 USA
California NanoSystems Institute, University of California, Los Angeles, CA, 90095 USA
E-mail: [email protected], [email protected]
Search for more papers by this authorCorresponding Author
Tian Xia
Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA, 90095 USA
California NanoSystems Institute, University of California, Los Angeles, CA, 90095 USA
E-mail: [email protected], [email protected]
Search for more papers by this authorXiang Wang
Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA, 90095 USA
California NanoSystems Institute, University of California, Los Angeles, CA, 90095 USA
Search for more papers by this authorChong Hyun Chang
California NanoSystems Institute, University of California, Los Angeles, CA, 90095 USA
Search for more papers by this authorJinhong Jiang
California NanoSystems Institute, University of California, Los Angeles, CA, 90095 USA
Search for more papers by this authorXiangsheng Liu
Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA, 90095 USA
Search for more papers by this authorJiulong Li
Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA, 90095 USA
Search for more papers by this authorQi Liu
Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA, 90095 USA
Search for more papers by this authorYu-Pei Liao
Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA, 90095 USA
Search for more papers by this authorLinjiang Li
California NanoSystems Institute, University of California, Los Angeles, CA, 90095 USA
Search for more papers by this authorCorresponding Author
André E. Nel
Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA, 90095 USA
California NanoSystems Institute, University of California, Los Angeles, CA, 90095 USA
E-mail: [email protected], [email protected]
Search for more papers by this authorCorresponding Author
Tian Xia
Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA, 90095 USA
California NanoSystems Institute, University of California, Los Angeles, CA, 90095 USA
E-mail: [email protected], [email protected]
Search for more papers by this authorAbstract
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, SiO2, and V2O5) exhibit cytotoxicity in both cell types, while SiO2 and V2O5 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 SiO2 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 V2O5 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.
Conflict of Interest
The authors declare no conflict of interest. IP developed by Dr. Nel was licensed to Westwood Bioscience and NAMMI Therapeutics by The Regents of UC. AN is co-founder, equity holder, and Executive Board member in Westwood Bioscience, Inc.
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