Skip to main content
SpringerLink
Log in

Mechanisms for how inhaled multiwalled carbon nanotubes suppress systemic immune function in mice

  • Article
  • Published:

From Nature Nanotechnology

View current issue Submit your manuscript

Abstract

The potential health effects of inhaling carbon nanotubes are important because of possible exposures in occupational settings. Previously, we have shown mice that have inhaled multiwalled carbon nanotubes have suppressed systemic immune function. Here, we show the mechanisms for this immune suppression. Mice were exposed to 0, 0.3 or 1 mg m−3 multiwalled carbon nanotubes for 6 h per day for 14 consecutive days in whole-body inhalation chambers. Only those exposed to a dose of 1 mg m−3 presented suppressed immune function; this involved activation of cyclooxygenase enzymes in the spleen in response to a signal from the lungs. Spleen cells from exposed animals partially recovered their immune function when treated with ibuprofen, a drug that blocks the formation of cyclooxygenase enzymes. Knockout mice without cyclooxygenase enzymes were not affected when exposed to multiwalled carbon nanotubes, further confirming the importance of this enzyme in suppression. Proteins from the lungs of exposed mice suppressed the immune function of spleen cells from normal mice, but not those from knockout mice. Our findings suggest that signals from the lung can activate signals in the spleen to suppress the immune function of exposed mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1: Immunosuppression is partially rescued by treatment with ibuprofen.
Figure 2: MWNT-induced immunosuppression is dependent on activation of the cyclooxygenase pathway.
Figure 3: Lavage fluid protein collected from MWNT-exposed (1 mg m−3) animals is capable of inducing immune dysfunction.
Figure 4: MWNTs induce TGFß release in the lung that activates prostaglandin E2 and IL-10 expression in splenocytes.
Figure 5

Similar content being viewed by others

References

  1. Stern, S. T. & McNeil, S. E. Nanotechnology safety concerns revisited. Toxicol. Sci. 101, 4–21 (2008).

    Article  CAS  Google Scholar 

  2. Lam, C. W., James, J. T., McCluskey, R. & Hunter, R. L. Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol. Sci. 77, 126–134 (2004).

    Article  CAS  Google Scholar 

  3. Muller, J. et al. Respiratory toxicity of multi-wall carbon nanotubes. Toxicol. Appl. Pharmacol. 207, 221–231 (2005).

    Article  CAS  Google Scholar 

  4. Shvedova, A. A. et al. Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am. J. Physiol. Lung Cell. Mol. Physiol. 289, L698–L708 (2005).

    Article  CAS  Google Scholar 

  5. Warheit, D. B. et al. Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats. Toxicol. Sci. 77, 117–125 (2004).

    Article  CAS  Google Scholar 

  6. Mitchell, L. A. et al. Pulmonary and systemic immune response to inhaled multiwalled carbon nanotubes. Toxicol. Sci. 100, 203–214 (2007).

    Article  CAS  Google Scholar 

  7. Li, J. G. et al. Comparative study of pathological lesions induced by multiwalled carbon nanotubes in lungs of mice by intratracheal instillation and inhalation. Environ. Toxicol. 22, 415–421 (2007).

    Article  CAS  Google Scholar 

  8. Deng, X. et al. Translocation and fate of multi-walled carbon nanotubes in vivo. Carbon 45, 1419–1424 (2007).

    Article  CAS  Google Scholar 

  9. Bide, R. W., Armour, S. J. & Yee, E. Allometric respiration/body mass data for animals to be used for estimates of inhalation toxicity to young adult humans. J. Appl. Toxicol. 20, 273–290 (2000).

    Article  CAS  Google Scholar 

  10. Miller, F. J. Dosimetry of particles in laboratory animals and humans in relationship to issues surrounding lung overload and human health risk assessment: a critical review. Inhal. Toxicol. 12, 19–57 (2000).

    Article  CAS  Google Scholar 

  11. Godwin, D. A., Wiley, C. J. & Felton, L. A. Using cyclodextrin complexation to enhance secondary photoprotection of topically applied ibuprofen. Eur. J. Pharm. Biopharm. 62, 85–93 (2006).

    Article  CAS  Google Scholar 

  12. Cheng, Y. S., Marshall, T. C., Henderson, R. F. & Newton, G. J. Use of a jet mill for dispersing dry powder for inhalation studies. Am. Ind. Hyg. Assoc. J. 46, 449–454 (1985).

    Article  CAS  Google Scholar 

  13. Maynard, A. D., Baron, P. A., Foley, M., Shvedova, A. A., Kisin, E. R. & Castranova, V. Exposure to carbon nanotube material: aerosol release during the handling of unrefined single-walled carbon nanotube material. Toxicol. Environ. Health A 67, 87–107 (2004).

    Article  CAS  Google Scholar 

  14. Beck-Speier, I. et al. Agglomerates of ultrafine particles of elemental carbon and TiO2 induce generation of lipid mediators in alveolar macrophages. Environ. Health Perspect. 109 (Suppl. 4), 613–618 (2001).

    CAS  Google Scholar 

  15. Burchiel, S. W. PGI2 and PGD2 effects on cyclic AMP and human T-cell mitogenesis. Prostaglandins Med. 3, 315–320 (1979).

    Article  CAS  Google Scholar 

  16. Chemnitz, J. M. et al. Prostaglandin E2 impairs CD4+ T-cell activation by inhibition of lck: implications in Hodgkin's lymphoma. Cancer Res. 66, 1114–1122 (2006).

    Article  CAS  Google Scholar 

  17. Choudhry, M. A. et al. Role of NFAT and AP-1 in PGE2-mediated T-cell suppression in burn injury. Shock 18, 212–216 (2002).

    Article  Google Scholar 

  18. Freire-de-Lima, C. G. et al. Apoptotic cells, through transforming growth factor-beta, coordinately induce anti-inflammatory and suppress pro-inflammatory eicosanoid and NO synthesis in murine macrophages. J. Biol. Chem. 281, 38376–38384 (2006).

    Article  CAS  Google Scholar 

  19. Kim, W. J., Kim, J. H. & Jang, S. K. Anti-inflammatory lipid mediator 15d-PGJ2 inhibits translation through inactivation of elF4A. EMBO J. 26, 5020–5032 (2007).

    Article  CAS  Google Scholar 

  20. Porter, D. W. et al. PGJ2 inhibition of LPS-induced inflammatory mediator expression from rat alveolar macrophages. J. Tox. Environ. Health 70, 1967–1976 (2007).

    Article  CAS  Google Scholar 

  21. Fionda, C., Nappi, F., Piccoli, M., Frati, L., Santoni, A. & Cippetelli, M. PGJ2 negatively regulated rankl gene expression in activated T lymphocytes: Role of NFkB and early growth response transcription factors. J. Immunol. 178, 4039–4050 (2007).

    Article  CAS  Google Scholar 

  22. Rajakariar, R. et al. Hematopoietic prostaglandin D2 synthase controls the onset and resolution of acute inflammation through PGD2 and 15-deoxy 12, 14, PGJ2. Proc. Natl Acad. Sci. USA 104, 20979–20984 (2007).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by NIEHS (P30 ES-012072) and EPA (RD-83252701).

Author information

Authors and Affiliations

  1. Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA

    L. A. Mitchell & J. D. McDonald

  2. University of New Mexico, Albuquerque, New Mexico, USA

    L. A. Mitchell, F. T. Lauer & S. W. Burchiel

Authors
  1. L. A. Mitchell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. T. Lauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. W. Burchiel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. D. McDonald
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

L.M. conceived and designed the experiments and wrote the article. L.M. and F.L. conducted the experiments. S.B. and J.M. contributed materials and analysis tools. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to J. D. McDonald.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mitchell, L., Lauer, F., Burchiel, S. et al. Mechanisms for how inhaled multiwalled carbon nanotubes suppress systemic immune function in mice. Nature Nanotech 4, 451–456 (2009). https://doi.org/10.1038/nnano.2009.151

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nnano.2009.151

  • Springer Nature Limited

This article is cited by

Search

Navigation