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Elife. 2015 Oct 5;4:e09623. doi: 10.7554/eLife.09623.

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

Author information

1
Department of Medicine, Baylor College of Medicine, Houston, United States.
2
Department of Pathology and Immunology, Baylor College of Medicine, Houston, United States.
3
Biology of Inflammation Center, Baylor College of Medicine, Houston, United States.
4
Department of Molecular Medicine, Beckman Research Institute, City of Hope National Medical Center, Duarte, United States.
5
Irell & Manella Graduate School of Biological Sciences, City of Hope National Medical Center, Duarte, United States.
6
Department of Chemistry, Rice University, Houston, United States.
7
Michael E. DeBakey VA Center, US Department of Veterans Affairs, 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.

KEYWORDS:

Th17; emphysema; human; human biology; immunology; inflammation; medicine; mouse

PMID:
26437452
PMCID:
PMC4612775
DOI:
10.7554/eLife.09623
[Indexed for MEDLINE]
Free PMC Article

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