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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 cell death compared with PEG-nCB.Lactate dehydrogenase (LDH) release from RAW 264.7 cells after 24 hr of the indicated treatment. Maximum LDH release was the amount of LDH released from lysed cells. ***p < 0.001 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.09623.018
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fig4s2: nCB-induced cell death compared with PEG-nCB.Lactate dehydrogenase (LDH) release from RAW 264.7 cells after 24 hr of the indicated treatment. Maximum LDH release was the amount of LDH released from lysed cells. ***p < 0.001 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.09623.018

Mentions: The previous findings demonstrated that when deposited in the lungs, nCB activates mDCs and induces durable Th17-dependent inflammation and emphysema in mice. To determine the mechanism of nCB-mediated lung pathology, we next investigated whether its physicochemical properties could account for its immunostimulatory function. Whether manufactured or found in the lungs of smokers with emphysema, nCB is very hydrophobic and completely insoluble in aqueous media. Conjugating polyethylene glycol to nCB (PEG-nCB) renders the material hydrophilic and miscible with aqueous solutions (Hwang et al., 2014). Mice challenged with intranasal PEG-nCB using the same protocol (Figure 2—figure supplement 1) failed to develop emphysema as assessed by quantitative CT-based lung volume measurements, MLI and microscopic evaluation of the lungs (Figure 4A,B,C). Further, we detected less anthracotic pigment in the lung parenchyma, suggesting that in contrast to hydrophobic nCB, PEG-nCB could be cleared from the lungs (Figure 4C). Microscopic inspection of isolated BAL fluid cells from PEG-nCB-challenged mice showed intact phagocytic cells compared to that of hydrophobic nCB, suggesting that the latter may induce less cytotoxic effects on phagocytic cells (Figure 4—figure supplement 1). In support of this, we found that the release of lactate dehydrogenase (LDH), an indicator of cytotoxicity, was enhanced in macrophage-like RAW 264.7 cells exposed to nCB as compared to PEG-nCB (Figure 4—figure supplement 2).10.7554/eLife.09623.016Figure 4.Hydrophobicity of nCB is important for its pathogenesis.


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 cell death compared with PEG-nCB.Lactate dehydrogenase (LDH) release from RAW 264.7 cells after 24 hr of the indicated treatment. Maximum LDH release was the amount of LDH released from lysed cells. ***p < 0.001 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.09623.018
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4612775&req=5

fig4s2: nCB-induced cell death compared with PEG-nCB.Lactate dehydrogenase (LDH) release from RAW 264.7 cells after 24 hr of the indicated treatment. Maximum LDH release was the amount of LDH released from lysed cells. ***p < 0.001 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.09623.018
Mentions: The previous findings demonstrated that when deposited in the lungs, nCB activates mDCs and induces durable Th17-dependent inflammation and emphysema in mice. To determine the mechanism of nCB-mediated lung pathology, we next investigated whether its physicochemical properties could account for its immunostimulatory function. Whether manufactured or found in the lungs of smokers with emphysema, nCB is very hydrophobic and completely insoluble in aqueous media. Conjugating polyethylene glycol to nCB (PEG-nCB) renders the material hydrophilic and miscible with aqueous solutions (Hwang et al., 2014). Mice challenged with intranasal PEG-nCB using the same protocol (Figure 2—figure supplement 1) failed to develop emphysema as assessed by quantitative CT-based lung volume measurements, MLI and microscopic evaluation of the lungs (Figure 4A,B,C). Further, we detected less anthracotic pigment in the lung parenchyma, suggesting that in contrast to hydrophobic nCB, PEG-nCB could be cleared from the lungs (Figure 4C). Microscopic inspection of isolated BAL fluid cells from PEG-nCB-challenged mice showed intact phagocytic cells compared to that of hydrophobic nCB, suggesting that the latter may induce less cytotoxic effects on phagocytic cells (Figure 4—figure supplement 1). In support of this, we found that the release of lactate dehydrogenase (LDH), an indicator of cytotoxicity, was enhanced in macrophage-like RAW 264.7 cells exposed to nCB as compared to PEG-nCB (Figure 4—figure supplement 2).10.7554/eLife.09623.016Figure 4.Hydrophobicity of nCB is important for its pathogenesis.

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