Skip to main content
SpringerLink
Log in

Priming of human neutrophils is necessary for their activation by extracellular DNA

  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Extracellular plasma DNA is thought to act as a damage-associated molecular pattern causing activation of immune cells. However, purified preparations of mitochondrial and nuclear DNA were unable to induce neutrophil activation in vitro. Thus, we examined whether granulocyte-macrophage colony-stimulating factor (GM-CSF) acting as a neutrophil priming agent can promote the activation of neutrophils by different types of extracellular DNA. GM-CSF pretreatment greatly increased p38 MAPK phosphorylation and promoted CD11b/CD66b expression in human neutrophils treated with mitochondrial and, to a lesser extent, with nuclear DNA. Our experiments clearly indicate that GM-CSFinduced priming of human neutrophils is necessary for their subsequent activation by extracellular DNA.

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

Similar content being viewed by others

Abbreviations

GM-CSF:

granulocyte-macrophage colony-stimulating factor

mtDNA:

mitochondrial DNA

nDNA:

nuclear DNA

References

  1. Piccinini, A. M., and Midwood, K. S. (2010) DAMPening inflammation by modulating TLR signalling, Mediators Inflamm., doi: 10.1155/2010/672395.

    Google Scholar 

  2. Kung, C. T., Hsiao, S. Y., Tsai, T. C., Su, C. M., Chang, W. N., Huang, C. R., Wang, H. C., Lin, W. C., Chang, H. W., Lin, Y. J., Cheng, B. C., Su, B. Y., Tsai, N. W., and Lu, C. H. (2012) Plasma nuclear and mitochondrial DNA levels as predictors of outcome in severe sepsis patients in the emergency room, J. Transl. Med., 10, 130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Tsai, N. W., Lin, T. K., Chen, S. D., Chang, W. N., Wang, H. C., Yang, T. M., Lin, Y. J., Jan, C. R., Huang, C. R., Liou, C. W., and Lu, C. H. (2011) The value of serial plasma nuclear and mitochondrial DNA levels in patients with acute ischemic stroke, Clin. Chim. Acta, 412, 476–479.

    Article  CAS  PubMed  Google Scholar 

  4. Arnalich, F., Maldifassi, M. C., Ciria, E., Codoceo, R., Renart, J., Fernandez-Capitan, C., Herruzo, R., GarciaRio, F., Lopez-Collazo, E., and Montiel, C. (2013) Plasma levels of mitochondrial and nuclear DNA in patients with massive pulmonary embolism in the emergency department: a prospective cohort study, Crit. Care, 17, R90.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Jahr, S., Hentze, H., Englisch, S., Hardt, D., Fackelmayer, F. O., Hesch, R.-D., and Knippers, R. (2001) DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells, Cancer Res., 61, 1659–1665.

    CAS  PubMed  Google Scholar 

  6. Gonzalez-Masia, J. A., Garcia-Olmo, D., and GarciaOlmo, D. C. (2013) Circulating nucleic acids in plasma and serum (CNAPS): applications in oncology, Onco Targets Ther., 6, 819–832.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Wang, L., Xie, L., Zhang, Q., Cai, X., Tang, Y., Hang, T., Liu, J., and Gong, J. (2015) Plasma nuclear and mitochondrial DNA levels in acute myocardial infarction patients, Coron. Artery Dis., 26, 296–300.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Yamanouchi, S., Kudo, D., Yamada, M., Miyagawa, N., Furukawa, H., and Kushimoto, S. (2013) Plasma mitochondrial DNA levels in patients with trauma and severe sepsis: time course and the association with clinical status, J. Crit. Care, 28, 1027–1031.

    Article  CAS  PubMed  Google Scholar 

  9. Nakahira, K., Hisata, S., and Choi, A. M. (2015) The roles of mitochondrial damage-associated molecular patterns in diseases, Antioxid. Redox Signal., 23, 1329–1350.

    Article  CAS  PubMed  Google Scholar 

  10. Mantovani, A., Cassatella, M. A., Costantini, C., and Jaillon, S. (2011) Neutrophils in the activation and regulation of innate and adaptive immunity, Nat. Rev. Immunol., 11, 519–531.

    Article  CAS  PubMed  Google Scholar 

  11. Zhang, Q., Raoof, M., Chen, Y., Sumi, Y., Sursal, T., Junger, W., Brohi, K., Itagaki, K., and Hauser, C. J. (2010) Circulating mitochondrial DAMPs cause inflammatory responses to injury, Nature, 464, 104–107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Prikhodko, A. S., Shabanov, A. K., Zinovkina, L. A., Popova, E. N., Aznauryan, M. A., Lanina, N. O., Vitushkina, M. V., and Zinovkin, R. A. (2015) Pure mitochondrial DNA does not activate human neutrophils in vitro, Biochemistry (Moscow), 80, 629–635.

    Article  CAS  Google Scholar 

  13. Collins, L. V., Hajizadeh, S., Holme, E., Jonsson, I. M., and Tarkowski, A. (2004) Endogenously oxidized mitochondrial DNA induces in vivo and in vitro inflammatory responses, J. Leukoc. Biol., 75, 995–1000.

    Article  CAS  PubMed  Google Scholar 

  14. Zhang, J. Z., Liu, Z., Liu, J., Ren, J. X., and Sun, T. S. (2014) Mitochondrial DNA induces inflammation and increases TLR9/NF-B expression in lung tissue, Int. J. Mol. Med., 33, 817–824.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Condliffe, A. M., Kitchen, E., and Chilvers, E. R. (1998) Neutrophil priming: pathophysiological consequences and underlying mechanisms, Clin. Sci. (London), 94, 461–471.

    Article  CAS  Google Scholar 

  16. Fuxman Bass, J. I., Alvarez, M. E., Gabelloni, M. L., Vermeulen, M. E., Amaral, M. M., Geffner, J. R., and Trevani, A. S. (2008) GM-CSF enhances a CpG-independent pathway of neutrophil activation triggered by bacterial DNA, Mol. Immunol., 46, 37–44.

    Article  CAS  PubMed  Google Scholar 

  17. King, M. P., and Attardi, G. (1996) Isolation of human cell lines lacking mitochondrial DNA, Methods Enzymol., 264, 304.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang, Q., Itagaki, K., and Hauser, C. J. (2010) Mitochondrial DNA is released by shock and activates neutrophils via p38 map kinase, Shock, 34, 55–59.

    Article  PubMed  Google Scholar 

  19. Bhagirath, V. C., Dwivedi, D. J., and Liaw, P. C. (2015) Comparison of the proinflammatory and procoagulant properties of nuclear, mitochondrial, and bacterial DNA, Shock, 44, 265–271.

    CAS  PubMed  Google Scholar 

  20. Simard, J. C., Noel, C., Tessier, P. A., and Girard, D. (2014) Human S100A9 potentiates IL-8 production in response to GM-CSF or fMLP via activation of a different set of transcription factors in neutrophils, FEBS Lett., 588, 2141–2146.

    Article  CAS  PubMed  Google Scholar 

  21. Itagaki, K., Kaczmarek, E., Lee, Y. T., Tang, I. T., Isal, B., Adibnia, Y., Sandler, N., Grimm, M. J., Segal, B. H., Otterbein, L. E., and Hauser, C. J. (2015) Mitochondrial DNA released by trauma induces neutrophil extracellular traps, PLoS One, 10, e0120549.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Hayashi, F., Means, T. K., and Luster, A. D. (2003) Tolllike receptors stimulate human neutrophil function, Blood, 102, 2660–2669.

    Article  CAS  PubMed  Google Scholar 

  23. Tsang, J. C., and Dennis Lo, Y. (2007) Circulating nucleic acids in plasma/serum, Pathology, 39, 197–207.

    Article  CAS  PubMed  Google Scholar 

  24. Pisetsky, D. S., and Fairhurst, A.-M. (2007) The origin of extracellular DNA during the clearance of dead and dying cells: review, Autoimmunity, 40, 281–284.

    Article  CAS  PubMed  Google Scholar 

  25. Paine, R., Standiford, T. J., Dechert, R. E., Moss, M., Martin, G. S., Rosenberg, A. L., Thannickal, V. J., Burnham, E. L., Brown, M. B., and Hyzy, R. C. (2012) A randomized trial of recombinant human granulocytemacrophage colony stimulating factor for patients with acute lung injury, Crit. Care Med., 40, 90–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lo, Y. D., Rainer, T. H., Chan, L. Y., Hjelm, N. M., and Cocks, R. A. (2000) Plasma DNA as a prognostic marker in trauma patients, Clin. Chem., 46, 319–323.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991, Moscow, Russia

    A. S. Prikhodko & L. A. Zinovkina

  2. Faculty of Biology, Lomonosov Moscow State University, 119991, Moscow, Russia

    M. V. Vitushkina & R. A. Zinovkin

  3. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991, Moscow, Russia

    E. N. Popova & R. A. Zinovkin

Authors
  1. A. S. Prikhodko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. V. Vitushkina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. A. Zinovkina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. N. Popova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. A. Zinovkin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. A. Zinovkin.

Additional information

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM16-043, April 3, 2016.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Prikhodko, A.S., Vitushkina, M.V., Zinovkina, L.A. et al. Priming of human neutrophils is necessary for their activation by extracellular DNA. Biochemistry Moscow 81, 609–614 (2016). https://doi.org/10.1134/S0006297916060079

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297916060079

Key words

Search

Navigation