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.

journal_name

Inhal Toxicol

journal_title

Inhalation toxicology

authors

Hamilton RF Jr,Buford M,Xiang C,Wu N,Holian A

doi

10.3109/08958378.2012.745633

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

995-1008

issue

14

eissn

0895-8378

issn

1091-7691

journal_volume

24

pub_type

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