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

  1. Ran You
  2. Wen Lu
  3. Ming Shan
  4. Jacob M Berlin
  5. Errol LG Samuel
  6. Daniela C Marcano
  7. Zhengzong Sun
  8. William KA Sikkema
  9. Xiaoyi Yuan
  10. Lizhen Song
  11. Amanda Y Hendrix
  12. James M Tour
  13. David Corry
  14. Farrah Kheradmand  Is a corresponding author
  1. Baylor College of Medicine, United States
  2. City of Hope National Medical Center, United States
  3. Rice University, United States
Research Article
  • Cited 34
  • Views 3,888
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Cite this article as: eLife 2015;4:e09623 doi: 10.7554/eLife.09623

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. Here 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.

Article and author information

Author details

  1. Ran You

    Department of Medicine, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Wen Lu

    Department of Medicine, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ming Shan

    Department of Medicine, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jacob M Berlin

    Department of Molecular Medicine, Beckman Research Institute, City of Hope National Medical Center, Duarte, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Errol LG Samuel

    Department of Chemistry, Rice University, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Daniela C Marcano

    Department of Chemistry, Rice University, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Zhengzong Sun

    Department of Chemistry, Rice University, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. William KA Sikkema

    Department of Chemistry, Rice University, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Xiaoyi Yuan

    Department of Medicine, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Lizhen Song

    Department of Medicine, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Amanda Y Hendrix

    Department of Medicine, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. James M Tour

    Department of Chemistry, Rice University, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. David Corry

    Department of Medicine, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Farrah Kheradmand

    Department of Medicine, Baylor College of Medicine, Houston, United States
    For correspondence
    farrahk@bcm.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: C57BL/6J mice were purchased from the Jackson Laboratory. ASC-/- mice (C57BL/6 background) were obtained from Dr. Vishva Dixit (Genentech, South San Francisco, CA). IL-17A-/- mice (C57BL/6 background) were obtained from Dr. Chen Dong (The University of Texas MD Anderson Cancer Center, Houston, TX). All mice were bred in the transgenic animal facility at Baylor College of Medicine. All experimental protocols(AN-4589) used in this study were approved by the Institutional Animal Care and Use Committee of Baylor College of Medicine and followed the National Research Council Guide for the Care and Use of Laboratory Animals.

Reviewing Editor

  1. Feng Shao, National Institute of Biological Sciences, China

Publication history

  1. Received: June 23, 2015
  2. Accepted: September 15, 2015
  3. Accepted Manuscript published: October 5, 2015 (version 1)
  4. Version of Record published: October 21, 2015 (version 2)

Copyright

© 2015, You et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Further reading

Further reading

  1. The elemental carbon in cigarette smoke causes inflammation and emphysema in the lung.

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