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Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema.

You R, Lu W, Shan M, Berlin JM, Samuel EL, Marcano DC, Sun Z, Sikkema WK, Yuan X, Song L, Hendrix AY, Tour JM, Corry DB, Kheradmand F - Elife (2015)

Bottom Line: The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known.Increasing the polarity or size of CB mitigated many adverse effects.Thus, nCB causes sterile inflammation, DSB, and emphysema and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Baylor College of Medicine, Houston, United States.

ABSTRACT
Chronic inhalation of cigarette smoke is the major cause of sterile inflammation and pulmonary emphysema. The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known. In this study, we show that insoluble nanoparticulate carbon black (nCB) accumulates in human myeloid dendritic cells (mDCs) from emphysematous lung and in CD11c(+) lung antigen presenting cells (APC) of mice exposed to smoke. Likewise, nCB intranasal administration induced emphysema in mouse lungs. Delivered by smoking or intranasally, nCB persisted indefinitely in mouse lung, activated lung APCs, and promoted T helper 17 cell differentiation through double-stranded DNA break (DSB) and ASC-mediated inflammasome assembly in phagocytes. Increasing the polarity or size of CB mitigated many adverse effects. Thus, nCB causes sterile inflammation, DSB, and emphysema and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers.

No MeSH data available.


Related in: MedlinePlus

nCB-induced strong lung inflammation compared with PEG-nCB.Multiplex analysis of pro-inflammatory cytokines and chemokines in lung homogenate of indicated groups. ***p < 0.001, **p < 0.01, *p < 0.1 as determined by the one-way ANOVA and Bonferroni's multiple comparison test. n = 5 per group. Data are mean ± SEM and representative of two independent studies.DOI:http://dx.doi.org/10.7554/eLife.09623.019
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fig4s3: nCB-induced strong lung inflammation compared with PEG-nCB.Multiplex analysis of pro-inflammatory cytokines and chemokines in lung homogenate of indicated groups. ***p < 0.001, **p < 0.01, *p < 0.1 as determined by the one-way ANOVA and Bonferroni's multiple comparison test. n = 5 per group. Data are mean ± SEM and representative of two independent studies.DOI:http://dx.doi.org/10.7554/eLife.09623.019

Mentions: Consistent with the failure to induce emphysema and cell death, exposure to PEG-nCB also resulted in attenuated recruitment of macrophages, neutrophils, and lymphocytes to the lung when compared with hydrophobic nCB (Figure 4D). This reduction in inflammation was accompanied by reduced expression of Mmp9 and Mmp12 transcripts in BAL fluid cells as compared with nCB-challenged mice (Figure 4E,F). The markedly reduced inflammatory nature of PEG-nCB was further underscored by the reduced concentrations of pro-inflammatory cytokines and chemokines detected from freshly collected lung homogenates of PEG-nCB-challenged mice (Figure 4—figure supplement 3), including decreased IL-6 and IL-1β levels (Figure 4G,H). Critically, PEG-nCB failed to induce lung Th17 cells when compared to nCB-exposed animals (Figure 4I,J). Thus, the pro-inflammatory potential of nCB is intimately tied to its hydrophobic surface and ability to induce cytotoxicity of phagocytic cells.


Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema.

You R, Lu W, Shan M, Berlin JM, Samuel EL, Marcano DC, Sun Z, Sikkema WK, Yuan X, Song L, Hendrix AY, Tour JM, Corry DB, Kheradmand F - Elife (2015)

nCB-induced strong lung inflammation compared with PEG-nCB.Multiplex analysis of pro-inflammatory cytokines and chemokines in lung homogenate of indicated groups. ***p < 0.001, **p < 0.01, *p < 0.1 as determined by the one-way ANOVA and Bonferroni's multiple comparison test. n = 5 per group. Data are mean ± SEM and representative of two independent studies.DOI:http://dx.doi.org/10.7554/eLife.09623.019
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4612775&req=5

fig4s3: nCB-induced strong lung inflammation compared with PEG-nCB.Multiplex analysis of pro-inflammatory cytokines and chemokines in lung homogenate of indicated groups. ***p < 0.001, **p < 0.01, *p < 0.1 as determined by the one-way ANOVA and Bonferroni's multiple comparison test. n = 5 per group. Data are mean ± SEM and representative of two independent studies.DOI:http://dx.doi.org/10.7554/eLife.09623.019
Mentions: Consistent with the failure to induce emphysema and cell death, exposure to PEG-nCB also resulted in attenuated recruitment of macrophages, neutrophils, and lymphocytes to the lung when compared with hydrophobic nCB (Figure 4D). This reduction in inflammation was accompanied by reduced expression of Mmp9 and Mmp12 transcripts in BAL fluid cells as compared with nCB-challenged mice (Figure 4E,F). The markedly reduced inflammatory nature of PEG-nCB was further underscored by the reduced concentrations of pro-inflammatory cytokines and chemokines detected from freshly collected lung homogenates of PEG-nCB-challenged mice (Figure 4—figure supplement 3), including decreased IL-6 and IL-1β levels (Figure 4G,H). Critically, PEG-nCB failed to induce lung Th17 cells when compared to nCB-exposed animals (Figure 4I,J). Thus, the pro-inflammatory potential of nCB is intimately tied to its hydrophobic surface and ability to induce cytotoxicity of phagocytic cells.

Bottom Line: The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known.Increasing the polarity or size of CB mitigated many adverse effects.Thus, nCB causes sterile inflammation, DSB, and emphysema and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Baylor College of Medicine, Houston, United States.

ABSTRACT
Chronic inhalation of cigarette smoke is the major cause of sterile inflammation and pulmonary emphysema. The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known. In this study, we show that insoluble nanoparticulate carbon black (nCB) accumulates in human myeloid dendritic cells (mDCs) from emphysematous lung and in CD11c(+) lung antigen presenting cells (APC) of mice exposed to smoke. Likewise, nCB intranasal administration induced emphysema in mouse lungs. Delivered by smoking or intranasally, nCB persisted indefinitely in mouse lung, activated lung APCs, and promoted T helper 17 cell differentiation through double-stranded DNA break (DSB) and ASC-mediated inflammasome assembly in phagocytes. Increasing the polarity or size of CB mitigated many adverse effects. Thus, nCB causes sterile inflammation, DSB, and emphysema and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers.

No MeSH data available.


Related in: MedlinePlus