title: Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema.
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.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, United States.|Department of Pathology and Immunology, Baylor College of Medicine, Houston, United States.|Biology of Inflammation Center, Baylor College of Medicine, Houston, United States.
authors.forename: Ran
authors.initials: R
authors.lastname: You
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, United States.|Department of Pathology and Immunology, Baylor College of Medicine, Houston, United States.|Biology of Inflammation Center, Baylor College of Medicine, Houston, United States.
authors.forename: Wen
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, United States.
authors.forename: Ming
authors.initials: M
authors.lastname: Shan
authors.affiliation: Department of Molecular Medicine, Beckman Research Institute, City of Hope National Medical Center, Duarte, United States.|Irell & Manella Graduate School of Biological Sciences, City of Hope National Medical Center, Duarte, United States.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Berlin
authors.affiliation: Department of Chemistry, Rice University, Houston, United States.
authors.forename: Errol Lg
authors.initials: EL
authors.lastname: Samuel
authors.affiliation: Department of Chemistry, Rice University, Houston, United States.
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Marcano
authors.affiliation: Department of Chemistry, Rice University, Houston, United States.
authors.forename: Zhengzong
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Chemistry, Rice University, Houston, United States.
authors.forename: William Ka
authors.initials: WK
authors.lastname: Sikkema
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, United States.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, United States.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, United States.
authors.forename: Amanda Y
authors.initials: AY
authors.lastname: Hendrix
authors.affiliation: Department of Chemistry, Rice University, Houston, United States.
authors.forename: James M
authors.initials: JM
authors.lastname: Tour
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, United States.|Department of Pathology and Immunology, Baylor College of Medicine, Houston, United States.|Biology of Inflammation Center, Baylor College of Medicine, Houston, United States.|Michael E. DeBakey VA Center, US Department of Veterans Affairs, Houston, United States.
authors.forename: David B
authors.initials: DB
authors.lastname: Corry
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, United States.|Department of Pathology and Immunology, Baylor College of Medicine, Houston, United States.|Biology of Inflammation Center, Baylor College of Medicine, Houston, United States.|Michael E. DeBakey VA Center, US Department of Veterans Affairs, Houston, United States.
authors.forename: Farrah
authors.initials: F
authors.lastname: Kheradmand
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000502:physiology; D053837:DNA Cleavage / Q000187:drug effects*; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced*; D051379:Mice; D053758:Nanoparticles / Q000633:toxicity*; D010586:Phagocytes / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000473:pathology*; D012906:Smoke; D012907:Smoking; D053260:Soot / Q000633:toxicity*; D058504:Th17 Cells / Q000187:drug effects / Q000502:physiology*
chemical_list: D058847:Inflammasomes; D012906:Smoke; D053260:Soot
keywords: Th17; emphysema; human; human biology; immunology; inflammation; medicine; mouse