title: NLRP3 inflammasome activation in murine alveolar macrophages and related lung pathology is associated with MWCNT nickel contamination.
abstract: Multi-walled carbon nanotubes (MWCNT) have been reported to cause lung pathologies in multiple studies. However, the mechanism responsible for the bioactivity has not been determined. This study used nine different well-characterized MWCNT and examined the outcomes in vitro and in vivo. MWCNT, from a variety of sources that differed primarily in overall purity and metal contaminants, were examined for their effects in vitro (toxicity and NLRP3 inflammasome activation using primary alveolar macrophages isolated from C57Bl/6 mice). In addition, in vivo exposures were conducted to determine the inflammatory and pathogenic potency. The particles produced a differential magnitude of responses, both in vivo and in vitro, that was associated most strongly with nickel contamination on the particle. Furthermore, the mechanism of action for the Ni-contaminated particles was in their ability to disrupt macrophage phagolysosomes, which resulted in NLRP3 activation and subsequent cytokine release associated with prolonged inflammation and lung pathology.
authors.affiliation: Center for Environmental Health Sciences, University of Montana, Missoula, USA.
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Hamilton
authors.forename: Mary
authors.initials: M
authors.lastname: Buford
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Xiang
authors.forename: Nianqiang
authors.initials: N
authors.lastname: Wu
authors.forename: Andrij
authors.initials: A
authors.lastname: Holian
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D058847:Inflammasomes / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D037742:Nanotubes, Carbon / Q000032:analysis / Q000633:toxicity*; D009532:Nickel / Q000032:analysis / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D061945:Caspase Inhibitors; D016207:Cytokines; D058847:Inflammasomes; D018836:Inflammation Mediators; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D037742:Nanotubes, Carbon; C492716:Nlrp3 protein, mouse; D009532:Nickel; D002401:Cathepsin B; C533915:Ctsb protein, mouse; D020170:Caspase 1