Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema
Ran You, Wen Lu, Ming Shan, Jacob M Berlin, Errol Lg Samuel, Daniela C Marcano, Zhengzong Sun, William Ka Sikkema, Xiaoyi Yuan, Lizhen Song, Amanda Y Hendrix, James M Tour, David B Corry, Farrah Kheradmand, Ran You, Wen Lu, Ming Shan, Jacob M Berlin, Errol Lg Samuel, Daniela C Marcano, Zhengzong Sun, William Ka Sikkema, Xiaoyi Yuan, Lizhen Song, Amanda Y Hendrix, James M Tour, David B Corry, Farrah Kheradmand
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.
Conflict of interest statement
The authors declare that no competing interests exist.
Figures
References
- Adam T, Mitschke S, Streibel T, Baker RR, Zimmermann R. Puff-by-puff resolved characterisation of cigarette mainstream smoke by single photon ionisation (SPI)-time-of-flight mass spectrometry (TOFMS): comparison of the 2R4F research cigarette and pure Burley, Virginia, Oriental and Maryland tobacco cigarettes. Analytica Chimica Acta. 2006;572:219–229. doi: 10.1016/j.aca.2006.05.043.
- Arif JM, Khan SG, Ashquin M, Rahman Q. Modulation of macrophage-mediated cytotoxicity by kerosene soot: possible role of reactive oxygen species. Environmental Research. 1993;61:232–238. doi: 10.1006/enrs.1993.1067.
- Baker RR. Temperature distribution inside a burning cigarette. Nature. 1974;247:405–406. doi: 10.1038/247405a0.
- Baker RR, Dixon M. The retention of tobacco smoke constituents in the human respiratory tract. Inhalation Toxicology. 2006;18:255–294. doi: 10.1080/08958370500444163.
- Barnes PJ. Cellular and molecular mechanisms of chronic obstructive pulmonary disease. Clinics in Chest Medicine. 2014;35:71–86. doi: 10.1016/j.ccm.2013.10.004.
- Bleck B, Tse DB, Jaspers I, Curotto de Lafaille MA, Reibman J. Diesel exhaust particle-exposed human bronchial epithelial cells induce dendritic cell maturation. The Journal of Immunology. 2006;176:7431–7437. doi: 10.4049/jimmunol.176.12.7431.
- Carter BD, Abnet CC, Feskanich D, Freedman ND, Hartge P, Lewis CE, Ockene JK, Prentice RL, Speizer FE, Thun MJ, Jacobs EJ. Smoking and mortality—beyond established causes. New England Journal of Medicine. 2015;372s:631–640. doi: 10.1056/NEJMc1503675#SA2.
- Chang Y, Al-Alwan L, Audusseau S, Chouiali F, Carlevaro-Fita J, Iwakura Y, Baglole CJ, Eidelman DH, Hamid Q. Genetic deletion of IL-17A reduces cigarette smoke-induced inflammation and alveolar type II cell apoptosis. American Journal of Physiology. 2014;306:L132–L143. doi: 10.1152/ajplung.00111.2013.
- Churg A, Myers JL, Tazelaar H, Wright JL. Thurlbeck's pathology of the lung. 3rd edition. New York, NY: Thieme; 2005.
- Churg A, Marshall CV, Sin DD, Bolton S, Zhou S, Thain K, Cadogan EB, Maltby J, Soars MG, Mallinder PR, Wright JL. Late intervention with a myeloperoxidase inhibitor stops progression of experimental chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine. 2012a;185:34–43. doi: 10.1164/rccm.201103-0468OC.
- Churg A, Zhou S, Wright JL. Series ‘matrix metalloproteinases in lung health and disease’: matrix metalloproteinases in COPD. European Respiratory Journal. 2012b;39:197–209. doi: 10.1183/09031936.00121611.
- Corry D, Kulkarni P, Lipscomb MF. The migration of bronchoalveolar macrophages into hilar lymph nodes. American Journal of Pathology. 1984;115:321–328.
- Cosio MG, Saetta M, Agusti A. Immunologic aspects of chronic obstructive pulmonary disease. New England Journal of Medicine. 2009;360:2445–2454. doi: 10.1056/NEJMra0804752.
- Dadvand P, Nieuwenhuijsen MJ, Agustí À, de Batlle J, Benet M, Beelen R, Cirach M, Martinez D, Hoek G, Basagaña X, Ferrer A, Ferrer J, Rodriguez-Roisin R, Sauleda J, Guerra S, Antó JM, Garcia-Aymerich J. Air pollution and biomarkers of systemic inflammation and tissue repair in COPD patients. European Respiratory Journal. 2014;44:603–613. doi: 10.1183/09031936.00168813.
- Eppert BL, Wortham BW, Flury JL, Borchers MT. Functional characterization of T cell populations in a mouse model of chronic obstructive pulmonary disease. The Journal of Immunology. 2013;190:1331–1340. doi: 10.4049/jimmunol.1202442.
- Eriksen M, Mackay J, Ross H. The Tobacco Atlas. 2014
- Franchi L, Nunez G. Immunology. Orchestrating inflammasomes. Science. 2012;337:1299–1300. doi: 10.1126/science.1229010.
- Furlaneto JA, Anderson AE, Jr, Foraker AG. Soot emphysema in a locomotive engineer. Archives of Environmental Health. 1969;18:1008–1013. doi: 10.1080/00039896.1969.10665527.
- Garza KM, Soto KF, Murr LE. Cytotoxicity and reactive oxygen species generation from aggregated carbon and carbonaceous nanoparticulate materials. International Journal of Nanomedicine. 2008;3:83–94. doi: 10.2217/17435889.3.1.83.
- Goswami S, Angkasekwinai P, Shan M, Greenlee KJ, Barranco WT, Polikepahad S, Seryshev A, Song LZ, Redding D, Singh B, Sur S, Woodruff P, Dong C, Corry DB, Kheradmand F. Divergent functions for airway epithelial matrix metalloproteinase 7 and retinoic acid in experimental asthma. Nature Immunology. 2009;10:496–503. doi: 10.1038/ni.1719.
- Guo Z, Deshpande R, Paull TT. ATM activation in the presence of oxidative stress. Cell Cycle. 2010;9:4805–4811. doi: 10.4161/cc.9.24.14323.
- Harwood LM, Moody CJ. Experimental organic chemistry: principles and practice. Hoboken, NJ: Wiley-Blackwell; 1989.
- Hwang CC, Ruan G, Wang L, Zheng H, Samuel EL, Xiang C, Lu W, Kasper W, Huang K, Peng Z, Schaefer Z, Kan AT, Martí AA, Wong MS, Tomson MB, Tour JM. Carbon-based nanoreporters designed for subsurface hydrogen sulfide detection. ACS Applied Materials and Interfaces. 2014;6:7652–7658. doi: 10.1021/am5009584.
- IARC Working Group on the Evaluation of Carcinogenic Risks to Humans . IARC monographs on the evaluation of carcinogenic risks to humans. Volume 93. Lyon, France: 2010. pp. 1–466.
- Kheradmand F, Shan M, Xu C, Corry D. Autoimmunity in chronic obstructive pulmonary disease: clinical and experimental evidence. Expert Review of Clinical Immunology. 2012;8:285–292. doi: 10.1586/eci.12.7.
- Kono H, Orlowski GM, Patel Z, Rock KL. The IL-1-dependent sterile inflammatory response has a substantial caspase-1-independent component that requires cathepsin C. Journal of Immunology. 2012;189:3734–3740. doi: 10.4049/jimmunol.1200136.
- Kurimoto E, Miyahara N, Kanehiro A, Waseda K, Taniguchi A, Ikeda G, Koga H, Nishimori H, Tanimoto Y, Kataoka M, Iwakura Y, Gelfand EW, Tanimoto M. IL-17A is essential to the development of elastase-induced pulmonary inflammation and emphysema in mice. Respiratory Research. 2013;14:5. doi: 10.1186/1465-9921-14-5.
- Li Y, Yang D. The ATM inhibitor KU-55933 suppresses cell proliferation and induces apoptosis by blocking Akt in cancer cells with overactivated Akt. Molecular Cancer Therapeutics. 2010;1:113–125. doi: 10.1158/1535-7163.MCT-08-1189.
- Lu W, You R, Yuan X, Yang T, Samuel EL, Marcano DC, Sikkema WK, Tour JM, Rodriguez A, Kheradmand F, Corry DB. MicroRNA-22 Inhibits histone Deacytylase 4 to promote t Helper-17 cell-dependent emphysema. Nature Immunology. 2015 doi: 10.1038/ni.3292.
- Lutz MB, Kukutsch N, Ogilvie AL, Rössner S, Koch F, Romani N, Schuler G. An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. Journal of Immunological Methods. 1999;223:77–92. doi: 10.1016/S0022-1759(98)00204-X.
- Mariathasan S, Newton K, Monack DM, Vucic D, French DM, Lee WP, Roose-Girma M, Erickson S, Dixit VM. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature. 2004;430:213–218. doi: 10.1038/nature02664.
- Merget R, Bauer T, Küpper HU, Philippou S, Bauer HD, Breitstadt R, Bruening T. Health hazards due to the inhalation of amorphous silica. Archives of Toxicology. 2002;75:625–634. doi: 10.1007/s002040100266.
- Mitchev K, Dumortier P, De Vuyst P. ‘Black Spots’ and hyaline pleural plaques on the parietal pleura of 150 urban necropsy cases. American Journal of Surgical Pathology. 2002;26:1198–1206. doi: 10.1097/00000478-200209000-00010.
- Newton R, Cambridge L, Hart LA, Stevens DA, Lindsay MA, Barnes PJ. The MAP kinase inhibitors, PD098059, UO126 and SB203580, inhibit IL-1beta-dependent PGE(2) release via mechanistically distinct processes. British Journal of Pharmacology. 2000;130:1353–1361. doi: 10.1038/sj.bjp.0703431.
- Oberdörster G, Oberdörster E, Oberdörster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environmental Health Perspectives. 2005;113:823–839. doi: 10.1289/ehp.7339.
- Perfetti TA, Rodgman A. The chemical components of tobacco and tobacco smoke. 2nd edition. Boca Raton, FL: CRC Press; 2013.
- Piccinini AM, Midwood KS. DAMPening inflammation by modulating TLR signalling. Mediators of Inflammation. 2010 doi: 10.1155/2010/672395.
- Pilla D, Kavadi AKM, Gurijala P, Masuram S, Delaney MS, Merchant ME, Sneddon J. Determination of selected chlorohydrocarbons and polyaromatic hydrocarbons by gas chromatography–mass spectrometry in soils in Southwest Louisiana. Microchemical Journal. 2009;91:13–15. doi: 10.1016/j.microc.2008.06.002.
- Pope CA, III, Burnett RT, Turner MC, Cohen A, Krewski D, Jerrett M, Gapstur SM, Thun MJ. Lung cancer and cardiovascular disease mortality associated with ambient air pollution and cigarette smoke: shape of the exposure-response relationships. Environmental Health Perspectives. 2011;119:1616–1621. doi: 10.1289/ehp.1103639.
- Reisetter AC, Stebounova LV, Baltrusaitis J, Powers L, Gupta A, Grassian VH, Monick MM. Induction of inflammasome-dependent pyroptosis by carbon black nanoparticles. Journal of Biological Chemistry. 2011;286:21844–21852. doi: 10.1074/jbc.M111.238519.
- Reynolds ES. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. The Journal of Cell Biology. 1963;17:208–212. doi: 10.1083/jcb.17.1.208.
- Sahu S, Timari M, Bhangare R, Pandit G. Particle size distribution of mainstream and Exhaled cigarette smoke and Predictive deposition in human respiratory tract. Aerosol and Air Quality Research. 2013;13:324–332.
- Salvi S. Tobacco smoking and environmental risk factors for chronic obstructive pulmonary disease. Clinics in Chest Medicine. 2014;35:17–27. doi: 10.1016/j.ccm.2013.09.011.
- Shan M, Cheng HF, Song LZ, Roberts L, Green L, Hacken-Bitar J, Huh J, Bakaeen F, Coxson HO, Storness-Bliss C, Ramchandani M, Lee SH, Corry DB, Kheradmand F. Lung myeloid dendritic cells coordinately induce TH1 and TH17 responses in human emphysema. Science Translational Medicine. 2009;1:4ra10. doi: 10.1126/scitranlsmed.3000154.
- Shan M, You R, Yuan X, Frazier MV, Porter P, Seryshev A, Hong JS, Song LZ, Zhang Y, Hilsenbeck S, Whitehead L, Zarinkamar N, Perusich S, Corry DB, Kheradmand F. Agonistic induction of PPAR reverses cigarette smoke-induced emphysema. Journal of Clinical Investigation. 2014;124:1371–1381. doi: 10.1172/JCI70587.
- Shan M, Yuan X, Song LZ, Roberts L, Zarinkamar N, Seryshev A, Zhang Y, Hilsenbeck S, Chang SH, Dong C, Corry DB, Kheradmand F. Cigarette smoke induction of osteopontin (SPP1) mediates T(H)17 inflammation in human and experimental emphysema. Science Translational Medicine. 2012;4:117ra119. doi: 10.1126/scitranslmed.3003041.
- Spurr AR. A low-viscosity epoxy resin embedding medium for electron microscopy. Journal of Ultrastructure Research. 1969;26:31–43. doi: 10.1016/S0022-5320(69)90033-1.
- Wang B, Ho SSH, Ho KF, Huang Y, Chan CS, Feng NSY. An environmental Chamber study of the characteristics of air Pollutants released from environmental tobacco smoke. Aerosol and Air Quality Research. 2012;12:1269–1281.
- Watson J, Chow J, Chen L. Summary of organic and elemental Carbon/Black carbon analysis methods and Intercomparisons. Aerosol and Air Quality Research. 2005;5:65–102.
- Watson ML. Staining of tissue sections for electron microscopy with heavy metals. The Journal of Biophysical and Biochemical Cytology. 1958;4:475–478. doi: 10.1083/jcb.4.4.475.
- Wilmore E, de Caux S, Sunter NJ, Tilby MJ, Jackson GH, Austin CA, Durkacz BW. A novel DNA-dependent protein kinase inhibitor, NU7026, potentiates the cytotoxicity of topoisomerase II poisons used in the treatment of leukemia. Blood. 2004;103:4659–4665. doi: 10.1182/blood-2003-07-2527.
- Zhang J, Chu S, Zhong X, Lao Q, He Z, Liang Y. Increased expression of CD4+IL-17+ cells in the lung tissue of patients with stable chronic obstructive pulmonary disease (COPD) and smokers. International Immunopharmacology. 2013;15:58–66. doi: 10.1016/j.intimp.2012.10.018.
- Zhou Y, Caron P, Legube G, Paull TT. Quantitation of DNA double-strand break resection intermediates in human cells. Nucleic Acids Research. 2014;42:e19. doi: 10.1093/nar/gkt1309.
Source: PubMed