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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 induces pro-inflammatory cytokines and chemokines in the lung.Concentration of pro-inflammatory cytokines and chemokines detected via MILLIPLEX Assay (Millipore, Billerica, MA) in the lung homogenate collected from mice in each group. n = 5 per group. ***p < 0.001, **p < 0.01, *p < 0.05 as determined by Student's t-test and data are mean ± SEM and representative of three independent experiments.DOI:http://dx.doi.org/10.7554/eLife.09623.006
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fig2s2: nCB induces pro-inflammatory cytokines and chemokines in the lung.Concentration of pro-inflammatory cytokines and chemokines detected via MILLIPLEX Assay (Millipore, Billerica, MA) in the lung homogenate collected from mice in each group. n = 5 per group. ***p < 0.001, **p < 0.01, *p < 0.05 as determined by Student's t-test and data are mean ± SEM and representative of three independent experiments.DOI:http://dx.doi.org/10.7554/eLife.09623.006

Mentions: 4 weeks after the last intranasal instillation of nCB, harvested lungs were extensively anthracotic, similar in appearance to lungs of long-term smokers (Figure 2A). Physiologically, the nCB challenge-induced enlargement of the alveolar spaces (Figure 2B) concomitant with significant increases in total lung volume quantified by micro-CT imaging and unbiased lung morphometry measurement (mean linear intercept; MLI) (Figure 2C,D), both hallmarks of emphysema. Mice exposed to nCB showed significantly increased numbers of macrophages, neutrophils, and lymphocytes in BAL fluid as compared to vehicle (PBS)-challenged control animals (Figure 2E). Consistently, increased lung inflammation was accompanied by higher concentrations of inflammatory cytokines and chemokines (Figure 2—figure supplement 2) as well as elastolytic matrix metalloproteinases (MMPs) 9 and 12 (Figure 2F), all of which are characteristic features of cigarette smoke-induced emphysema in human patients and animal models of this disease (Shan et al., 2009; Churg et al., 2012a). Similarly, both lung parenchymal CD11c+ mDCs and BAL fluid macrophages showed an accumulation of nCB as detected by hyperspectral imaging (Figure 2G–I).10.7554/eLife.09623.004Figure 2.Carbon black-induced emphysema mouse model.


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 induces pro-inflammatory cytokines and chemokines in the lung.Concentration of pro-inflammatory cytokines and chemokines detected via MILLIPLEX Assay (Millipore, Billerica, MA) in the lung homogenate collected from mice in each group. n = 5 per group. ***p < 0.001, **p < 0.01, *p < 0.05 as determined by Student's t-test and data are mean ± SEM and representative of three independent experiments.DOI:http://dx.doi.org/10.7554/eLife.09623.006
© Copyright Policy
Related In: Results  -  Collection

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

fig2s2: nCB induces pro-inflammatory cytokines and chemokines in the lung.Concentration of pro-inflammatory cytokines and chemokines detected via MILLIPLEX Assay (Millipore, Billerica, MA) in the lung homogenate collected from mice in each group. n = 5 per group. ***p < 0.001, **p < 0.01, *p < 0.05 as determined by Student's t-test and data are mean ± SEM and representative of three independent experiments.DOI:http://dx.doi.org/10.7554/eLife.09623.006
Mentions: 4 weeks after the last intranasal instillation of nCB, harvested lungs were extensively anthracotic, similar in appearance to lungs of long-term smokers (Figure 2A). Physiologically, the nCB challenge-induced enlargement of the alveolar spaces (Figure 2B) concomitant with significant increases in total lung volume quantified by micro-CT imaging and unbiased lung morphometry measurement (mean linear intercept; MLI) (Figure 2C,D), both hallmarks of emphysema. Mice exposed to nCB showed significantly increased numbers of macrophages, neutrophils, and lymphocytes in BAL fluid as compared to vehicle (PBS)-challenged control animals (Figure 2E). Consistently, increased lung inflammation was accompanied by higher concentrations of inflammatory cytokines and chemokines (Figure 2—figure supplement 2) as well as elastolytic matrix metalloproteinases (MMPs) 9 and 12 (Figure 2F), all of which are characteristic features of cigarette smoke-induced emphysema in human patients and animal models of this disease (Shan et al., 2009; Churg et al., 2012a). Similarly, both lung parenchymal CD11c+ mDCs and BAL fluid macrophages showed an accumulation of nCB as detected by hyperspectral imaging (Figure 2G–I).10.7554/eLife.09623.004Figure 2.Carbon black-induced emphysema mouse model.

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