title: Gold nanoparticles induce apoptosis, endoplasmic reticulum stress events and cleavage of cytoskeletal proteins in human neutrophils.
abstract: Gold nanoparticles (AuNPs) are promising candidates for developing nanomedicines, for the treatment of different disorders, including inflammatory diseases. However, how AuNPs could alter the biology of human neutrophils, key player cells in inflammation, is a poorly documented area of research. Here we found that, although AuNP of 20 nm (AuNP20) could be internalized in cytosolic vacuoles but that AuNP70 were localized at the cell membrane, both induced apoptosis similarly by a caspase-dependent mechanism. AuNPs induced degradation of the cytoskeletal proteins vimentin, lamin B1 and gelsolin, but, unexpectedly, did not increase their cell surface expression. Consequent with caspase-4 processing, AuNPs were found to activate endoplasmic reticulum (ER)-stress, as evidenced by activation of the three ER sensors, IRE1 (inositol-requiring protein-1), ATF-6 (activating transcription factor-6) and PERK (protein kinase RNA (PKR)-like ER kinase). AuNPs are novel human neutrophil proapoptotic agents indicating that they are toxic to these cells. However, the fact that they do not induce cell surface expression of cytoskeletal proteins could decrease potential adverse effects and toxicity of AuNPs by limiting, for example, the production of autoantibody against cytoskeleton components.
authors.affiliation: Laboratoire de recherche en inflammation et physiologie des granulocytes, Université du Québec, Institut National de la Recherche Scientifique (INRS)-Institut Armand-Frappier, Laval, Québec, Canada.
authors.forename: Claudie
authors.initials: C
authors.lastname: Noël
authors.affiliation: Laboratoire de recherche en inflammation et physiologie des granulocytes, Université du Québec, Institut National de la Recherche Scientifique (INRS)-Institut Armand-Frappier, Laval, Québec, Canada.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Simard
authors.affiliation: Laboratoire de recherche en inflammation et physiologie des granulocytes, Université du Québec, Institut National de la Recherche Scientifique (INRS)-Institut Armand-Frappier, Laval, Québec, Canada. Electronic address: Denis.girard@iaf.inrs.ca.
authors.forename: Denis
authors.initials: D
authors.lastname: Girard
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006046:Gold / Q000494:pharmacology*; D006801:Humans; D053768:Metal Nanoparticles / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D006046:Gold; D020169:Caspases
keywords: Apoptosis; Caspases; Cytoskeleton; Endoplasmic reticulum; Gold nanoparticles; Neutrophils