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.
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.
- Feng Shao, National Institute of Biological Sciences, China
© 2015, You et al.
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