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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

Schematic representation of nCB-induced lung inflammation and emphysema protocol.Mice were lightly anesthetized with isoflurane and challenged with 50 µl of 107 ng/ml of CB or vehicle (PBS with 1% sucrose) twice weekly for 6 weeks; 4 weeks following the last challenge, mice underwent CT scan of chest and were euthanized.DOI:http://dx.doi.org/10.7554/eLife.09623.005
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fig2s1: Schematic representation of nCB-induced lung inflammation and emphysema protocol.Mice were lightly anesthetized with isoflurane and challenged with 50 µl of 107 ng/ml of CB or vehicle (PBS with 1% sucrose) twice weekly for 6 weeks; 4 weeks following the last challenge, mice underwent CT scan of chest and were euthanized.DOI:http://dx.doi.org/10.7554/eLife.09623.005

Mentions: We have previously recapitulated smoke-induced lung sterile inflammation and emphysema by adoptively transferring lineage-negative CD11c+ mDCs isolated from the lungs of smoke-exposed mice to naive mice, which revealed the direct, causal role of mDCs in emphysema (Shan et al., 2012). As we found that these mDCs contained nCB, we sought to determine if nCB was alone sufficient to induce emphysema. We first determined that the commercial nCB does not desorb polycyclic aromatic hydrocarbons (PAHs), as determined by Soxhlet extraction followed by gas chromatography mass spectroscopy (GCMS) (Harwood and Moody, 1989). Mice were then exposed twice weekly for 6 weeks to hydrocarbon free, hydrophobic, neutral surface charged nCB (average particle size 15 nm), to achieve a total lung dose of ∼1% of wet lung weight (mg/g), which approximates human lung nCB burdens (Figure 2—figure supplement 1).


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)

Schematic representation of nCB-induced lung inflammation and emphysema protocol.Mice were lightly anesthetized with isoflurane and challenged with 50 µl of 107 ng/ml of CB or vehicle (PBS with 1% sucrose) twice weekly for 6 weeks; 4 weeks following the last challenge, mice underwent CT scan of chest and were euthanized.DOI:http://dx.doi.org/10.7554/eLife.09623.005
© Copyright Policy
Related In: Results  -  Collection

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

fig2s1: Schematic representation of nCB-induced lung inflammation and emphysema protocol.Mice were lightly anesthetized with isoflurane and challenged with 50 µl of 107 ng/ml of CB or vehicle (PBS with 1% sucrose) twice weekly for 6 weeks; 4 weeks following the last challenge, mice underwent CT scan of chest and were euthanized.DOI:http://dx.doi.org/10.7554/eLife.09623.005
Mentions: We have previously recapitulated smoke-induced lung sterile inflammation and emphysema by adoptively transferring lineage-negative CD11c+ mDCs isolated from the lungs of smoke-exposed mice to naive mice, which revealed the direct, causal role of mDCs in emphysema (Shan et al., 2012). As we found that these mDCs contained nCB, we sought to determine if nCB was alone sufficient to induce emphysema. We first determined that the commercial nCB does not desorb polycyclic aromatic hydrocarbons (PAHs), as determined by Soxhlet extraction followed by gas chromatography mass spectroscopy (GCMS) (Harwood and Moody, 1989). Mice were then exposed twice weekly for 6 weeks to hydrocarbon free, hydrophobic, neutral surface charged nCB (average particle size 15 nm), to achieve a total lung dose of ∼1% of wet lung weight (mg/g), which approximates human lung nCB burdens (Figure 2—figure supplement 1).

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