Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema
- Baylor College of Medicine, United States
- City of Hope National Medical Center, United States
- Rice University, 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. 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
Reviewing Editor
- Feng Shao, National Institute of Biological Sciences, China
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.
Version history
- Received: June 23, 2015
- Accepted: September 15, 2015
- Accepted Manuscript published: October 5, 2015 (version 1)
- 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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Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema
eLife 4:e09623.
https://doi.org/10.7554/eLife.09623
Further reading
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The elemental carbon in cigarette smoke causes inflammation and emphysema in the lung.
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- Cell Biology
- Immunology and Inflammation
Cytokine polyfunctionality is a well-established concept in immune cells, especially T cells, and their ability to concurrently produce multiple cytokines has been associated with better immunological disease control and subsequent effectiveness during infection and disease. To date, only little is known about the secretion dynamics of those cells, masked by the widespread deployment of mainly time-integrated endpoint measurement techniques that do not easily differentiate between concurrent and sequential secretion. Here, we employed a single-cell microfluidic platform capable of resolving the secretion dynamics of individual PBMCs. To study the dynamics of poly-cytokine secretion, as well as the dynamics of concurrent and sequential polyfunctionality, we analyzed the response at different time points after ex vivo activation. First, we observed the simultaneous secretion of cytokines over the measurement time for most stimulants in a subpopulation of cells only. Second, polyfunctionality generally decreased with prolonged stimulation times and revealed no correlation with the concentration of secreted cytokines in response to stimulation. However, we observed a general trend towards higher cytokine secretion in polyfunctional cells, with their secretion dynamics being distinctly different from mono-cytokine-secreting cells. This study provided insights into the distinct secretion behavior of heterogenous cell populations after stimulation with well-described agents and such a system could provide a better understanding of various immune dynamics in therapy and disease.
