NLRP3 inflammasome activation in murine alveolar macrophages and related lung pathology is associated with MWCNT nickel contamination

Hamilton, Raymond F.; Buford, Mary; Xiang, Chengcheng; Wu, Nianqiang; Holian, Andrij

doi:10.3109/08958378.2012.745633

Cited by 98 publications

(98 citation statements)

References 35 publications

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“…The inflammatory mediators IL-1β and TNF-α are putatively involved in the adverse bioreactivity of carbon nanotubes with macrophages. 29,30 However, following treatment of AMs with MWCNTs used in the present study, we did not observe any differences in the release of these mediators compared to the nontreated control AMs (data not shown). This may be due to the fact that we did not treat these AMs with priming agents, such as lipopolysaccharide, which in unpublished studies we have found to be necessary; thus the associated inflammasome pathway may not have been activated.…”

Section: Discussioncontrasting

confidence: 45%

Functional consequences for primary human alveolar macrophages following treatment with long, but not short, multiwalled carbon nanotubes

Sweeney¹,

Grandolfo²,

Ruenraroengsak³

et al. 2015

IJN

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Purpose: Multiwalled carbon nanotubes (MWCNTs) are a potential human health hazard, primarily via inhalation. In the lung, alveolar macrophages (AMs) provide the first line of immune cellular defense against inhaled materials. We hypothesized that, 1 and 5 days after treating AMs with short (0.6 μm in length; MWCNT-0.6 μm) and long (20 μm in length; MWCNT-20 μm) MWCNTs for 24 hours, AMs would exhibit increased markers of adverse bioreactivity (cytokine release and reactive oxygen species generation) while also having a modified functional ability (phagocytosis and migration). Methods: Primary human AMs were treated with short and long MWCNTs for 24 hours, 1 and 5 days after which toxicity end points, including cell death, reactive oxygen species generation, and inflammatory mediator release, were measured. AM functional end points involving phagocytic ability and migratory capacity were also measured. Results: AM viability was significantly decreased at 1 and 5 days after treatment with MWCNT-20 μm, while superoxide levels and inflammatory mediator release were significantly increased. At the same time, there was reduced phagocytosis and migratory capacity alongside increased expression of MARCO; this coincided with frustrated phagocytosis observed by scanning electron microscopy. In contrast, the adverse bioreactivity of the shorter MWCNT-0.6 μm with AMs (and any resulting reduction in AM functional ability) was substantially less marked or absent altogether. Conclusion:This study shows that after 24-hour treatment with long, but not short, MWCNTs, AM function is severely affected up to 5 days after the initial exposure. This has potentially significant pathophysiological consequences for individuals who may be intentionally (via therapeutic applications) or unintentionally exposed to these nanomaterials.

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Section: Discussioncontrasting

confidence: 45%

Functional consequences for primary human alveolar macrophages following treatment with long, but not short, multiwalled carbon nanotubes

Sweeney¹,

Grandolfo²,

Ruenraroengsak³

et al. 2015

IJN

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“…However, the high demand for these materials, in concert with their toxicity potential, may pose a future health risk for humans. Pulmonary exposure studies in murine models have revealed that MWCNT exposure has negative consequences, including chronic inflammation leading to granuloma formation and fibrosis, along with asthma-like pathology (Glista-Baker et al, 2014; Hamilton et al, 2007, 2012, 2013; Mercer et al, 2011, 2013). The mechanisms that promote chronic inflammation are not clear, but activation of the NLRP3 inflammasome in macrophages and IL-1β signaling has been shown to be necessary for MWCNT-induced inflammation (Girtsman et al, 2012; Hamilton et al, 2012; Palomaki et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…The MWCNT used in this study has previously been shown to induce a robust inflammatory and pathological response (Girtsman et al, 2012; Hamilton et al, 2012). The potential of extracellular HMGB1 to act on primary AM is of particular focus in this study since previous findings report strong correlations between AM production of IL-1β and pathology score following MWCNT exposure (Hamilton et al, 2012). Furthermore, caspase-1 −/− mice were used to assess the contribution of NLRP3 Inflammasome activation to HMGB1 secretion.…”

Section: Introductionmentioning

confidence: 99%

Extracellular HMGB1 regulates multi-walled carbon nanotube-induced inflammation in vivo

Jessop

Holian

2014

Nanotoxicology

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Endotoxin is often used to activate NF-κB in vitro when assessing NLRP3 inflammasome activation by various exogenous particles including nanoparticles. However, the endogenous source of this signal 1 is unknown. High-mobility group box 1 (HMGB1) is known to play a critical role in acute lung injury, however the potential contribution of the alarmin HMGB1 to NLRP3 Inflammasome activation has not been determined in response to nanoparticles in vivo. In this study, the ability of multi-walled carbon nanotubes (MWCNT) to cause release of HMGB1 in vitro and in vivo, as well as the potential of HMGB1 to function as signal 1 in vitro and in vivo, was determined. HMGB1 activity in vivo was assessed by administration of HMGB1 neutralization antibodies following MWCNT exposure. Caspase-1−/− mice were utilized to elucidate the dependence of HMGB1 secretion on NLRP3 inflammasome activity. MWCNT exposure increased extracellular HMGB1 levels in primary alveolar macrophages from C57Bl/6 mice and C10 mouse epithelial cell culture supernatants, and in C57Bl/6 mouse lung lavage fluid. MWCNT-induced HMGB1 secretion was dependent upon caspase-1. HMGB1 increased MWCNT-induced IL-1β release from macrophages in vitro, and neutralization of extracellular HMGB1 reduced MWCNT-induced IL-1β secretion in vivo. HMGB1 neutralization was accompanied with overall decreased inflammation. In summary, this study suggests extracellular HMGB1 participates in NLRP3 inflammasome activity and regulates IL-1β associated sterile inflammation induced by MWCNT.

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“…19 Ni 2+ contamination of multi-walled CNTs is related to particle bioactivity and is correlated with NLRP3 inflammasome activation. 20 However, whether NLRP3 inflammasome activation participates in NiONP-induced IL-1β release and pulmonary inflammation is unclear. Furthermore, the mechanisms of the NP-mediated activation of the NLRP3 inflammasome remain elusive.…”

Section: Introductionmentioning

confidence: 99%

Exposure to nickel oxide nanoparticles induces pulmonary inflammation through NLRP3 inflammasome activation in rats

Cao¹,

Fang²,

Lu³

et al. 2016

IJN

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With recent advances in the manufacture and application of nickel oxide nanoparticles (NiONPs), concerns about their adverse effects on the respiratory system are increasing. However, the underlying cellular and molecular mechanisms of NiONP-induced pulmonary toxicity remain unclear. In this study, we focused on the impacts of NiONPs on pulmonary inflammation and investigated whether the NLRP3 inflammasome is involved in NiONP-induced pulmonary inflammation and injury. NiONP suspensions were administered by single intratracheal instillation to rats, and inflammatory responses were evaluated at 3 days, 7 days, or 28 days after treatment. NiONP exposure resulted in sustained pulmonary inflammation accompanied by inflammatory cell infiltration, alveolar proteinosis, and cytokine secretion. Expression of Nlrp3 was markedly upregulated by the NiONPs, which was accompanied by overexpression of the active form of caspase-1 (p20) and interleukin (IL)-1β secretion in vivo. NiONP-induced IL-1β secretion was partially prevented by co-treatment with a caspase-1 inhibitor in macrophages. Moreover, siRNA-mediated Nlrp3 knockdown completely attenuated NiONP-induced cytokine release and caspase-1 activity in macrophages in vitro. In addition, NiONP-induced NLRP3 inflammasome activation requires particle uptake and reactive oxygen species production. Collectively, our findings suggest that the NLRP3 inflammasome participates in NiONP-induced pulmonary inflammation and offer new strategies to combat the pulmonary toxicity induced by NiONPs.

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NLRP3 inflammasome activation in murine alveolar macrophages and related lung pathology is associated with MWCNT nickel contamination

Cited by 98 publications

References 35 publications

Functional consequences for primary human alveolar macrophages following treatment with long, but not short, multiwalled carbon nanotubes

Functional consequences for primary human alveolar macrophages following treatment with long, but not short, multiwalled carbon nanotubes

Extracellular HMGB1 regulates multi-walled carbon nanotube-induced inflammation in vivo

Exposure to nickel oxide nanoparticles induces pulmonary inflammation through NLRP3 inflammasome activation in rats

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