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A single intratracheal instillation of single-walled carbon nanotubes induced early lung fibrosis and subchronic tissue damage in mice

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Abstract

Large amounts of nanomaterials may reach both the natural and occupational environments. This represents a potential health hazard. People have forecasted that CNTs may lead to the toxicity such as mesothelioma and fibrosis like asbestos. To identify dominant immune responses induced by SWCNTs, we investigated the composition of bronchioalveolar lavage (BAL) cells, the secretion of cytokine and collagen, histopathology, protein expression, and cell phenotypes over time after a single administration of single-walled carbon nanotubes (SWCNT). In our results, the number of total cells and macrophages remained at the up-regulated level until Day 28, neutrophils rapidly increased at Day 1, and lymphocytes increased from Day 7. In the BAL fluid, pro-inflammatory cytokines rapidly increased at Day 1 and remained at an up-regulated level throughout the experimental period. IL-12 and IL-10 rapidly increased at Day 1 after administration and remained at a similar level until Day 28. IFN-γ and IL-4 reached the maximum at Day 1, and IL-5, TGF-β, and collagen reached the maximum at Day 7. IL-13 and IL-17 increased in a time-dependent manner. The distribution of B cells and cytotoxic T cells markedly increased at Days 7 and 14, and fibrotic lesions were histopathologically observed at Days 7 and 14. The expressions of caspase-3, p53, COL1A1, COX-2, iNOS, MMP-9, and MMP-2 were also markedly increased at Days 7 and 14. In addition, the expression of mesothelin, iNOS, MMP-9, and p53 was up-regulated until Day 28. Based on these findings, we suggest that a single intratracheal instillation of SWCNTs may induce early lung fibrosis and subchronic tissue damage.

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References

  • Chang K, Pastan I (1996) Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers. Proc Natl Acad Sci USA 93(1):136–143

    Article  PubMed  CAS  Google Scholar 

  • Chou CC, Hsiao HY, Hong QS, Chen CH, Peng YW, Chen HW, Yang PC (2008) Single-walled carbon nanotubes can induce pulmonary injury in mouse model. Nano Lett 8(2):437–445

    Article  PubMed  CAS  Google Scholar 

  • Cutroneo KR (2007) TGF-beta-induced fibrosis and SMAD signaling: oligo decoys as natural therapeutics for inhibition of tissue fibrosis and scarring. Wound Repair Regen 15(Suppl 1):S54–S60

    Article  PubMed  Google Scholar 

  • Donaldson K, Murphy FA, Duffin R, Poland CA (2010) Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma. Part Fibre Toxicol 7:5

    Article  PubMed  Google Scholar 

  • Folkmann JK, Risom L, Jacobsen NR, Wallin H, Loft S, Møller P (2009) Oxidatively damaged DNA in rats exposed by oral gavage to C60 fullerenes and single-walled carbon nanotubes. Environ Health Perspect 117(5):703–708

    PubMed  CAS  Google Scholar 

  • Hassan R, Ho M (2008) Mesothelin targeted cancer immunotherapy. Eur J Cancer 44(1):46–53

    Article  PubMed  CAS  Google Scholar 

  • Herzog E, Byrne HJ, Casey A, Davoren M, Lenz AG, Maier KL, Duschl A, Oostingh GJ (2009) SWCNT suppress inflammatory mediator responses in human lung epithelium in vitro. Toxicol Appl Pharmacol 234(3):378–390

    Article  PubMed  CAS  Google Scholar 

  • Inoue K, Takano H, Koike E, Yanagisawa R, Sakurai M, Tasaka S, Ishizaka A, Shimada A (2008) Effects of pulmonary exposure to carbon nanotubes on lung and systemic inflammation with coagulatory disturbance induced by lipopolysaccharide in mice. Exp Biol Med (Maywood) 233(12):1583–1590

    Article  CAS  Google Scholar 

  • Kagan VE, Tyurina YY, Tyurin VA, Konduru NV, Potapovich AI, Osipov AN, Kisin ER, Schwegler-Berry D, Mercer R, Castranova V, Shvedova AA (2006) Direct and indirect effects of single walled carbon nanotubes on RAW 264.7 macrophages: role of iron. Toxicol Lett 165(1):88–100

    Article  PubMed  CAS  Google Scholar 

  • Karsenty G, Park RW (1995) Regulation of type I collagen genes expression. Int Rev Immunol 12(2–4):177–185

    Article  PubMed  CAS  Google Scholar 

  • Kershenobich Stalnikowitz D, Weissbrod AB (2003) Liver fibrosis and inflammation. A review. Ann Hepatol 2(4):159–163

    PubMed  Google Scholar 

  • Lam CW, James JT, McCluskey R, Arepalli S, Hunter RL (2006) A review of carbon nanotube toxicity and assessment of potential occupational and environmental health risks. Crit Rev Toxicol 36(3):189–217

    Article  PubMed  CAS  Google Scholar 

  • Lawrence DA (1996) Transforming growth factor-beta: a general review. Eur Cytokine Netw 7(3):363–374

    PubMed  CAS  Google Scholar 

  • Manna SK, Sarkar S, Barr J, Wise K, Barrera EV, Jejelowo O, Rice-Fichtg AC, Ramesh GT (2005) Single-walled carbon nanotube induces oxidative stress and activates nuclear transcription factor-kappaB in human keratinocytes. Nano Lett 5(9):1676–1684

    Article  PubMed  CAS  Google Scholar 

  • Maynard AD, Baron PA, Foley M, Shvedova AA, Kisin ER, Castranova V (2004) Exposure to carbon nanotube material: aerosol release during the handling of unrefined single-walled carbon nanotube material. J Toxicol Environ Health A 67(1):87–107

    Article  PubMed  CAS  Google Scholar 

  • Murray AR, Kisin E, Leonard SS, Young SH, Kommineni C, Kagan VE, Castranova V, Shvedova AA (2009) Oxidative stress and inflammatory response in dermal toxicity of single-walled carbon nanotubes. Toxicology 257(3):161–171

    Article  PubMed  CAS  Google Scholar 

  • Nygaard UC, Hansen JS, Samuelsen M, Alberg T, Marioara CD, Løvik M (2009) Single-walled and multi-walled carbon nanotubes promote allergic immune responses in mice. Toxicol Sci 109(1):113–123

    Article  PubMed  CAS  Google Scholar 

  • Pacurari M, Yin XJ, Zhao J, Ding M, Leonard SS, Schwegler-Berry D, Ducatman BS, Sbarra D, Hoover MD, Castranova V, Vallyathan V (2008) Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappaB, and Akt in normal and malignant human mesothelial cells. Environ Health Perspect 116(9):1211–1217

    Article  PubMed  CAS  Google Scholar 

  • Park EJ, Cho WS, Jeong J, Yi J, Choi K, Park K (2009a) Pro-inflammatory and potential allergic responses resulting from B cell activation in mice treated with multi-walled carbon nanotubes by intratracheal instillation. Toxicology 259:113–121

    Google Scholar 

  • Park EJ, Yoon J, Choi K, Yi J, Park K (2009b) Induction of chronic inflammation in mice treated with titanium dioxide nanoparticles by intratracheal instillation. Toxicology 260:37–46

    Google Scholar 

  • Sakamoto Y, Nakae D, Fukumori N, Tayama K, Maekawa A, Imai K, Hirose A, Nishimura T, Ohashi N, Ogata A (2009) Induction of mesothelioma by a single intrascrotal administration of multi-wall carbon nanotube in intact male Fischer 344 rats. J Toxicol Sci 34(1):65–76

    Article  PubMed  CAS  Google Scholar 

  • Sharma CS, Sarkar S, Periyakaruppan A, Barr J, Wise K, Thomas R, Wilson BL, Ramesh GT (2007) Single-walled carbon nanotubes induces oxidative stress in rat lung epithelial cells. J Nanosci Nanotechnol. 7(7):2466–2472

    Article  PubMed  CAS  Google Scholar 

  • Shvedova AA, Kagan VE (2010) The role of nanotoxicology in realizing the ‘helping without harm’ paradigm of nanomedicine: lessons from studies of pulmonary effects of single-walled carbon nanotubes. J Intern Med 267(1):106–118

    Article  PubMed  CAS  Google Scholar 

  • Shvedova AA, Kisin ER, Mercer R, Murray AR, Johnson VJ, Potapovich AI, Tyurina YY, Gorelik O, Arepalli S, Schwegler-Berry D, Hubbs AF, Antonini J, Evans DE, Ku BK, Ramsey D, Maynard A, Kagan VE, Castranova V, Baron P (2005) Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am J Physiol Lung Cell Mol Physiol 289(5):L698–L708

    Article  PubMed  CAS  Google Scholar 

  • Shvedova AA, Fabisiak JP, Kisin ER, Murray AR, Roberts JR, Tyurina YY, Antonini JM, Feng WH, Kommineni C, Reynolds J, Barchowsky A, Castranova V, Kagan VE (2008a) Sequential exposure to carbon nanotubes and bacteria enhances pulmonary inflammation and infectivity. Am J Respir Cell Mol Biol 38(5):579–590

    Article  PubMed  CAS  Google Scholar 

  • Shvedova AA, Kisin ER, Murray AR, Kommineni C, Castranova V, Fadeel B, Kagan VE (2008b) Increased accumulation of neutrophils and decreased fibrosis in the lung of NADPH oxidase-deficient C57BL/6 mice exposed to carbon nanotubes. Toxicol Appl Pharmacol 231(2):235–240

    Article  PubMed  CAS  Google Scholar 

  • Silva IA, Graber J, Nyland JF, Silbergeld EK (2005) In vitro HgCl2 exposure of immune cells at different stages of maturation: effects on phenotype and function. Environ Res 98:341–348

    Google Scholar 

  • Song Y, Li X, Du X (2009) Exposure to nanoparticles is related to pleural effusion, pulmonary fibrosis and granuloma. Eur Respir J 34(3):559–567

    Article  PubMed  CAS  Google Scholar 

  • Takagi A, Hirose A, Nishimura T, Fukumori N, Ogata A, Ohashi N, Kitajima S, Kanno J (2008) Induction of mesothelioma in p53 ± mouse by intraperitoneal application of multi-wall carbon nanotube. J Toxicol Sci 33(1):105–116

    Article  PubMed  CAS  Google Scholar 

  • Vendrame M, Gemma C, Pennypacker KR, Bickford PC, Davis SC, Sanberg PR, Willing AE (2006) Cord blood rescues stroke-induced changes in splenocyte phenotype and function. Exp Neurol 199:191–200

    Google Scholar 

  • Warheit DB, Laurence BR, Reed KL, Roach DH, Reynolds GA, Webb TR (2004) Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats. Toxicol Sci 77(1):117–125

    Article  PubMed  CAS  Google Scholar 

  • Wei G, Zhou H, Liu Z, Song Y, Wang L, Sun L, Li Z (2005) One-step synthesis of silver nanoparticles, nanorods, and nanowires on the surface of DNA network. J Phys Chem B 109:8738–8743

    Article  PubMed  CAS  Google Scholar 

  • Witasp E, Shvedova AA, Kagan VE, Fadeel B (2009) Single-walled carbon nanotubes impair human macrophage engulfment of apoptotic cell corpses. Inhal Toxicol 21(Suppl 1):131–136

    Article  PubMed  CAS  Google Scholar 

  • Yang CM, Park JS, An KH, Lim SC, Seo K, Kim B, Park KA, Han S, Park CY, Lee YH (2005) Selective removal of metallic single-walled carbon nanotubes with small diameters by using nitric and sulfuric acids. J Phys Chem B 109(41):19242–19248

    Article  PubMed  CAS  Google Scholar 

  • Yu X, Zhang J, Choi W, Choi JY, Kim JM, Gan L, Liu Z (2010) Nano Lett 10(9):3343–3349

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Ministry of Environment as the Eco-technopia 21 project and National Institute of Environmental Research.

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Correspondence to Eun-Jung Park.

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Park, EJ., Roh, J., Kim, SN. et al. A single intratracheal instillation of single-walled carbon nanotubes induced early lung fibrosis and subchronic tissue damage in mice. Arch Toxicol 85, 1121–1131 (2011). https://doi.org/10.1007/s00204-011-0655-8

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  • DOI: https://doi.org/10.1007/s00204-011-0655-8

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