Molecular and Cellular Biochemistry

, Volume 352, Issue 1–2, pp 57–63

Cellular cytotoxic response induced by highly purified multi-wall carbon nanotube in human lung cells

Article

Abstract

Carbon nanotubes, a promising nanomaterial with unique characteristics, have applications in a variety of fields. The cytotoxic effects of carbon nanotubes are partially due to the induction of oxidative stress; however, the detailed mechanisms of nanotube cytotoxicity and their interaction with cells remain unclear. In this study, the authors focus on the acute toxicity of vapor-grown carbon fiber, HTT2800, which is one of the most highly purified multi-wall carbon nanotubes (MWCNT) by high-temperature thermal treatment. The authors exposed human bronchial epithelial cells (BEAS-2B) to HTT2800 and measured the cellular uptake, mitochondrial function, cellular LDH release, apoptotic signaling, reactive oxygen species (ROS) generation and pro-inflammatory cytokine release. The HTT2800-exposed cells showed cellular uptake of the carbon nanotube, increased cell death, enhanced DNA damage, and induced cytokine release. However, the exposed cells showed no obvious intracellular ROS generation. These cellular and molecular findings suggest that HTT2800 could cause a potentially adverse inflammatory response in BEAS-2B cells.

Keywords

Multi-wall carbon nanotube Cellular uptake Cytokine release Bronchial epithelial cells Necrosis 

References

  1. 1.
    Bianco A, Kostarelos K, Prato M (2005) Applications of carbon nanotubes in drug delivery. Curr Opin Chem Biol 9(6):674–679. doi:10.1016/j.cbpa.2005.10.005 PubMedCrossRefGoogle Scholar
  2. 2.
    Takizawa H (2004) Diesel exhaust particles and their effect on induced cytokine expression in human bronchial epithelial cells. Curr Opin Allergy Clin Immunol 4(5):355–359.PubMedCrossRefGoogle Scholar
  3. 3.
    Haniu H, Matsuda Y, Takeuchi K, Kim YA, Hayashi T, Endo M (2010) Proteomics-based safety evaluation of multi-walled carbon nanotubes. Toxicol Appl Pharmacol 242(3):256–262. doi:10.1016/j.taap.2009.10.015 PubMedCrossRefGoogle Scholar
  4. 4.
    Herzog E, Byrne HJ, Davoren M, Casey A, Duschl A, Oostingh GJ (2009) Dispersion medium modulates oxidative stress response of human lung epithelial cells upon exposure to carbon nanomaterial samples. Toxicol Appl Pharmacol 236(3):276–281. doi:10.1016/j.taap.2009.02.007 PubMedCrossRefGoogle Scholar
  5. 5.
    Cui D, Tian F, Ozkan CS, Wang M, Gao H (2005) Effect of single wall carbon nanotubes on human hek293 cells. Toxicol Lett 155(1):73–85. doi:10.1016/j.toxlet.2004.08.015 PubMedCrossRefGoogle Scholar
  6. 6.
    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. doi:10.1016/j.taap.2008.10.015 PubMedCrossRefGoogle Scholar
  7. 7.
    Ke Y, Reddel RR, Gerwin BI, Miyashita M, McMenamin M, Lechner JF, Harris CC (1988) Human bronchial epithelial cells with integrated sv40 virus t antigen genes retain the ability to undergo squamous differentiation. Differentiation 38(1):60–66PubMedCrossRefGoogle Scholar
  8. 8.
    Endo M (1998) Grow carbon fibers in the vapor phase. Chem Tech 18:568–576Google Scholar
  9. 9.
    Endo M, Strano M, Ajayan P (2008) Potential applications of carbon nanotubes. Carbon Nanotubes 111:13–61CrossRefGoogle Scholar
  10. 10.
    Saito N, Usui Y, Aoki K, Narita N, Shimizu M, Hara K, Ogiwara N, Nakamura K, Ishigaki N, Kato H, Taruta S, Endo M (2009) Carbon nanotubes: biomaterial applications. Chem Soc Rev 38(7):1897–1903. doi:10.1039/b804822n PubMedCrossRefGoogle Scholar
  11. 11.
    Li M, Beg AA (2000) Induction of necrotic-like cell death by tumor necrosis factor alpha and caspase inhibitors: novel mechanism for killing virus-infected cells. J Virol 74(16):7470–7477PubMedCrossRefGoogle Scholar
  12. 12.
    Fotakis G, Timbrell JA (2006) In vitro cytotoxicity assays: comparison of ldh, neutral red, mtt and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicol Lett 160(2):171–177. doi:10.1016/j.toxlet.2005.07.001 PubMedCrossRefGoogle Scholar
  13. 13.
    Hamid R, Rotshteyn Y, Rabadi L, Parikh R, Bullock P (2004) Comparison of alamar blue and mtt assays for high through-put screening. Toxicol In Vitro 18(5):703–710. doi:10.1016/j.tiv.2004.03.012 PubMedCrossRefGoogle Scholar
  14. 14.
    McIlroy D, Sakahira H, Talanian RV, Nagata S (1999) Involvement of caspase 3-activated dnase in internucleosomal DNA cleavage induced by diverse apoptotic stimuli. Oncogene 18(31):4401–4408. doi:10.1038/sj.onc.1202868 PubMedCrossRefGoogle Scholar
  15. 15.
    Guillot L, Medjane S, Le-Barillec K, Balloy V, Danel C, Chignard M, Si-Tahar M (2004) Response of human pulmonary epithelial cells to lipopolysaccharide involves toll-like receptor 4 (tlr4)-dependent signaling pathways: evidence for an intracellular compartmentalization of tlr4. J Biol Chem 279(4):2712–2718. doi:10.1074/jbc.M305790200 PubMedCrossRefGoogle Scholar
  16. 16.
    Kam NW, Dai H (2005) Carbon nanotubes as intracellular protein transporters: generality and biological functionality. J Am Chem Soc 127(16):6021–6026. doi:10.1021/ja050062v PubMedCrossRefGoogle Scholar
  17. 17.
    Shi Kam NW, Jessop TC, Wender PA, Dai H (2004) Nanotube molecular transporters: internalization of carbon nanotube-protein conjugates into mammalian cells. J Am Chem Soc 126(22):6850–6851. doi:10.1021/ja0486059 PubMedCrossRefGoogle Scholar
  18. 18.
    Canal-Raffin M, L’Azou B, Martinez B, Sellier E, Fawaz F, Robinson P, Ohayon-Courtes C, Baldi I, Cambar J, Molimard M, Moore N, Brochard P (2007) Physicochemical characteristics and bronchial epithelial cell cytotoxicity of folpan 80 wg(r) and myco 500(r), two commercial forms of folpet. Part Fibre Toxicol 4:8. doi:10.1186/1743-8977-4-8 PubMedCrossRefGoogle Scholar
  19. 19.
    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. doi:10.1289/ehp.10924 PubMedCrossRefGoogle Scholar
  20. 20.
    Dick CA, Brown DM, Donaldson K, Stone V (2003) The role of free radicals in the toxic and inflammatory effects of four different ultrafine particle types. Inhal Toxicol 15(1):39–52. doi:10.1080/08958370304454 PubMedCrossRefGoogle Scholar
  21. 21.
    Neveu WA, Allard JL, Raymond DM, Bourassa LM, Burns SM, Bunn JY, Irvin CG, Kaminsky DA, Rincon M (2010) Elevation of il-6 in the allergic asthmatic airway is independent of inflammation but associates with loss of central airway function. Respir Res 11:28. doi:10.1186/1465-9921-11-28 PubMedCrossRefGoogle Scholar
  22. 22.
    Shaker SB, von Wachenfeldt KA, Larsson S, Mile I, Persdotter S, Dahlback M, Broberg P, Stoel B, Bach KS, Hestad M, Fehniger TE, Dirksen A (2008) Identification of patients with chronic obstructive pulmonary disease (copd) by measurement of plasma biomarkers. Clin Respir J 2(1):17–25. doi:10.1111/j.1752-699X.2007.00032.x PubMedCrossRefGoogle Scholar
  23. 23.
    Gabay C, Kushner I (1999) Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340(6):448–454PubMedCrossRefGoogle Scholar
  24. 24.
    Cesta MF, Ryman-Rasmussen JP, Wallace DG, Masinde T, Hurlburt G, Taylor AJ, Bonner JC (2009) Bacterial lipopolysaccharide enhances pdgf signaling and pulmonary fibrosis in rats exposed to carbon nanotubes. Am J Respir Cell Mol Biol. doi: 10.1165/rcmb.2009-0113OC
  25. 25.
    Drost EM, Skwarski KM, Sauleda J, Soler N, Roca J, Agusti A, MacNee W (2005) Oxidative stress and airway inflammation in severe exacerbations of copd. Thorax 60(4):293–300. doi:10.1136/thx.2004.027946 PubMedCrossRefGoogle Scholar
  26. 26.
    Takeda N, Sumi Y, Prefontaine D, Al Abri J, Al Heialy N, Al-Ramli W, Michoud MC, Martin JG, Hamid Q (2009) Epithelium-derived chemokines induce airway smooth muscle cell migration. Clin Exp Allergy 39(7):1018–1026. doi:10.1111/j.1365-2222.2009.03238.x PubMedCrossRefGoogle Scholar
  27. 27.
    Toews GB (2001) Cytokines and the lung. Eur Respir J Suppl 34:3s–17sPubMedCrossRefGoogle Scholar
  28. 28.
    Akbulut H, Celik I, Akbulut A (2007) Cytokine levels in patients with brucellosis and their relations with the treatment. Indian J Med Microbiol 25(4):387–390PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  1. 1.Department of Integrative Physiology and Bio-System ControlShinshu University School of MedicineNaganoJapan
  2. 2.Institute of Carbon Science and TechnologyShinshu UniversityNaganoJapan

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