Skip to main content
Springer Nature Link
Log in

Evaluation of human macrophage functional state by voltammetric monitoring of nitrite ions

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

The method for assessing the level of nitric oxide (II) (NO) by voltammetric monitoring of nitrite ions was carried out on models M1 and M2 of polarized macrophages induced from monocytes of human peripheral blood with the addition of lipopolysaccharide (LPS) and interleukin-4 (IL-4), respectively. The model of induction of M1 and M2 macrophages was used in the work to achieve the corresponding shifts in the functional status of studied cells. Ethyl nitrite (EtONO) was used as a standard compound of nitrite ions for electrochemical measurements. Electrochemical determination of nitrite ions was performed by anodic linear sweep voltammetry in the first-order derivative mode (ALSV FOD) in Britton-Robinson (BR) buffer with pH 4.02 on carbon ink modified graphite electrode. EtONO calibrations were linear over a concentration range from 2 to 9 μmol L−1 with corresponding regression equation y = 0.768c − 0.048. Limit of detection (LOD) (S/N = 3) was 0.38 μmol L−1. The results of the study showed the fundamental possibility of using voltammetry to assess indirectly the production of nitric oxide by cells in supernatants of the monocytic macrophage lineage. The level of nitric oxide metabolites (nitrite ions) in supernatants was associated with the functional state of macrophages.

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

Access this article

Log in via an institution

Subscribe and save

Springer+
from $39.99 /Month
  • Starting from 10 chapters or articles per month
  • Access and download chapters and articles from more than 300k books and 2,500 journals
  • Cancel anytime
View plans

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Explore related subjects

Discover the latest articles, books and news in related subjects, suggested using machine learning.

References

  1. Ziegler-Heitbrock L. Blood monocytes and their subsets in health and disease. In: Biswas SK, Mantovani A, editors. Macrophages: biology and role in the pathology of diseases. New York: Springer Science+Business Media; 2014. p. 3–36.

    Chapter  Google Scholar 

  2. Galdiero MR, Biswas SK, Mantovani A. Polarized activation of macrophages. In: Biswas SK, Mantovani A, editors. Macrophages: biology and role in the pathology of diseases. New York: Springer Science+Business Media; 2014. p. 37–58.

    Chapter  Google Scholar 

  3. Galván-Peña S, O’Neill LAJ. Metabolic reprogramming in macrophage polarization. Front Immunol. 2014;5:1–6.

    Google Scholar 

  4. Lee M, Rey K, Besler K, Wang C, Choy J. Immunobiology of nitric oxide and regulation of inducible nitric oxide synthase. In: Kubiak JZ, editor. Results and problems in cell differentiation. Heidelberg: Springer-Verlag; 2017. p. 187–207.

    Google Scholar 

  5. Wink DA, Kasprzak KS, Maragos CM, Elespuru RK, Misra M, Dunams TM, et al. DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Am Assoc Adv Sci. 1991;254:1001–3.

    CAS  Google Scholar 

  6. Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JS, Tannenbaum SR. DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci U S A. 1992;89:3030–4.

    Article  CAS  Google Scholar 

  7. Szabó C. DNA strand breakage and activation of poly-ADP ribosyltransferase: a cytotoxic pathway triggered by peroxynitrite. Free Radic Biol Med. 1996;21:855–69.

    Article  Google Scholar 

  8. Korkmaz A, Oter S, Seyrek M, Topal T. Molecular, genetic and epigenetic pathways of peroxynitrite-induced cellular toxicity. Interdiscip Toxicol. 2009;2:219–28.

    Article  Google Scholar 

  9. Niles JC, Wishnok JS, Tannenbaum SR. Peroxynitrite-induced oxidation and nitration products of guanine and 8-oxoguanine: structures and mechanisms of product formation. Nitric Oxide Biol Chem. 2006;14:109–21.

    Article  CAS  Google Scholar 

  10. Wink DA, Mitchell JB. Chemical biology of nitric oxide: insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Radic Biol Med. 1998;25:434–56.

    Article  CAS  Google Scholar 

  11. Yadav R, Samuni Y, Abramson A, Zeltser R, Casap N, Kabiraj TK, et al. Pro-oxidative synergic bactericidal effect of NO: kinetics and inhibition by nitroxides. Free Radic Biol Med. 2014;67:248–54.

    Article  CAS  Google Scholar 

  12. Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM. M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol. 2000;164(12):6166–73.

    Article  CAS  Google Scholar 

  13. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004;25:677–86.

    Article  CAS  Google Scholar 

  14. Munder M, Eichmann K, Morán JM, Centeno F, Soler G, Modolell M. Th1/Th2-regulated expression of arginase isoforms in murine macrophages and dendritic cells. J Immunol. 1999;163:3771–7.

    CAS  PubMed  Google Scholar 

  15. Gordon S, Helming L, Martinez Estrada FO. Alternative activation of macrophages: concepts and prospects. In: Biswas SK, Mantovani A, editors. Macrophages: biology and role in the pathology of diseases. New York: Springer Science+Business Media; 2014. p. 59–76.

    Chapter  Google Scholar 

  16. Kzhyshkowska J, Mamidi S, Gratchev A, Kremmer E, Schmuttermaier C, Krusell L, et al. Novel stabilin-1 interacting chitinase-like protein (SI-CLP) is up-regulated in alternatively activated macrophages and secreted via lysosomal pathway. Blood. 2006;107:3221–8.

    Article  CAS  Google Scholar 

  17. Gratchev A, Schmuttermaier C, Mamidi S, Gooi LM, Goerdt S, Kzhyshkowska J. Expression of osteoarthritis marker YKL-39 is stimulated by transforming growth factor beta (TGF-beta) and IL-4 in differentiating macrophages. Biomark Insights. 2008;3:39–44.

    Article  CAS  Google Scholar 

  18. Mosser DM, Stewart CA. Regulatory macrophages and the maintenance of homeostasis. In: Biswas SK, Mantovani A, editors. Macrophages: biology and role in the pathology of diseases. New York: Springer Science+Business Media; 2014. p. 77–90.

    Chapter  Google Scholar 

  19. Butler AR, Flitney FW, Williams DLH. NO, nitrosonium ions, nitroxide ions, nitrosothiols and iron-nitrosyls in biology: a chemist’s perspective. Trends Pharmacol Sci. 1995;16:18–22.

    Article  CAS  Google Scholar 

  20. Gaston B. Nitric oxide and thiol groups. Biochim Biophys Acta Bioenerg. 1999;1411:323–33.

    Article  CAS  Google Scholar 

  21. Sies H. Oxidative stress: from basic research to clinical application. Am J Med. 1991;91:S31–8.

    Article  Google Scholar 

  22. Liu X, Miller MJS, Joshi MS, Thomas DD, Lancaster JR. Accelerated reaction of nitric oxide with O2 within the hydrophobic interior of biological membranes. Proc Natl Acad Sci U S A. 1998;95:2175–9.

    Article  CAS  Google Scholar 

  23. Iverson NM, Hofferber EM, Stapleton JA. Nitric oxide sensors for biological applications. Chemosensors. 2018;6:2–13.

    Article  Google Scholar 

  24. Miranda KM, Espey MG. Wink DA.A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide. 2009;5:62–71.

    Article  Google Scholar 

  25. Burke AJ, Sullivan FJ, Giles FJ, Glynn SA. The yin and yang of nitric oxide in cancer progression. Carcinogenesis. 2013;34:503–12.

    Article  CAS  Google Scholar 

  26. Ghanei-Motlagh M, Taher MA. A novel electrochemical sensor based on silver/halloysite nanotube/molybdenum disulfide nanocomposite for efficient nitrite sensing. Biosens Bioelectron. 2018;109:279–85.

    Article  CAS  Google Scholar 

  27. Huang SS, Liu L, Mei LP, Zhou JY, Guo FY, Wang AJ, et al. Electrochemical sensor for nitrite using a glassy carbon electrode modified with gold-copper nanochain networks. Microchim Acta. 2016;183:791–7.

    Article  CAS  Google Scholar 

  28. Bagheri H, Hajian A, Rezaei M, Shirzadmehr A. Composite of Cu metal nanoparticles-multiwall carbon nanotubes-reduced graphene oxide as a novel and high performance platform of the electrochemical sensor for simultaneous determination of nitrite and nitrate. J Hazard Mater. 2017;324:762–72.

    Article  CAS  Google Scholar 

  29. Liu L, Du J, Liu W e, Guo Y, Wu G, Qi W, et al. Enhanced His@AuNCs oxidase-like activity by reduced graphene oxide and its application for colorimetric and electrochemical detection of nitrite. Anal Bioanal Chem. 2019;411:2189–200.

    Article  CAS  Google Scholar 

  30. Radhakrishnan S, Krishnamoorthy K, Sekar C, Wilson J, Kim SJ. A highly sensitive electrochemical sensor for nitrite detection based on Fe2O3 nanoparticles decorated reduced graphene oxide nanosheets. Appl Catal B Environ. 2014;148–149:22–8.

    Article  Google Scholar 

  31. Yosypchuk B, Barek J, Fojta M. Carbon powder based films on traditional solid electrodes as an alternative to disposable electrodes. Electroanalysis. 2006;18:1126–30.

    Article  CAS  Google Scholar 

  32. Reinartz S, Schumann T, Finkernagel F, Wortmann A, Jansen JM, Meissner W, et al. Mixed-polarization phenotype of ascites-associated macrophages in human ovarian carcinoma: correlation of CD163 expression, cytokine levels and early relapse. Int J Cancer. 2014;134:32–42.

    Article  Google Scholar 

  33. Albina JE. On the expression of nitric oxide synthase by human macrophages. Why no NO? J Leukoc Biol. 1995;58:643–9.

    Article  CAS  Google Scholar 

  34. Gross TJ, Kremens K, Powers LS, Brink B, Knutson T, Domann FE, et al. Epigenetic silencing of the human NOS2 gene: rethinking the role of nitric oxide in human macrophage inflammatory responses. J Immunol. 2014;192:2326–38.

    Article  CAS  Google Scholar 

  35. Glair EWS, Wilkinson WE, Lang T, Sanders L, Misukonis MA, Gilkeson GS, et al. Increased expression of blood mononuclear cell nitric oxide synthase type 2 in rheumatoid arthritis patients. J Exp Med. 1996;184:1173–8.

    Article  Google Scholar 

  36. Anstey NM, Weinberg JB, Hassanali MY, Mwaikambo ED, Manyenga D, Misukonis MA, et al. Nitric oxide in Tanzanian children with malaria: inverse relationship between malaria severity and nitric oxide production/nitric oxide synthase type 2 expression. J Exp Med. 1996;184:557–67.

    Article  CAS  Google Scholar 

  37. Landes MB, Rajaram MVS, Nguyen H, Schlesinger LS. Role for NOD2 in mycobacterium tuberculosis -induced iNOS expression and NO production in human macrophages. J Leukoc Biol. 2015;97:1111–9.

    Article  CAS  Google Scholar 

Download references

Funding

Tomsk Polytechnic University Competitiveness Enhancement Program VIU-SESE-143/2019 supported this investigation. JB received financial support from Grant Agency of the Czech Republic (the Czech Science Foundation) (Project No. 17-03868S).

Author information

Authors and Affiliations

  1. National Research Tomsk Polytechnic University, Lenin Avenue 30, Tomsk, 634050, Russia

    Valentina Popova, Elena Korotkova, Jiri Barek & Marina Stakheyeva

  2. Department of Analytical Chemistry, Faculty of Science, UNESCO Laboratory of Environmental Electrochemistry, Charles University, Albertov 6, 12843, Prague 2, Czech Republic

    Jiri Barek

  3. Tomsk NRMC, Cancer Research Institute, Kooperativnyi str. 5, Tomsk, 634050, Russia

    Marina Stakheyeva, Anton Fedorov, Marina Patysheva & Olga Cheremisina

Authors
  1. Valentina Popova
    View author publications

    Search author on:PubMed Google Scholar

  2. Elena Korotkova
    View author publications

    Search author on:PubMed Google Scholar

  3. Jiri Barek
    View author publications

    Search author on:PubMed Google Scholar

  4. Marina Stakheyeva
    View author publications

    Search author on:PubMed Google Scholar

  5. Anton Fedorov
    View author publications

    Search author on:PubMed Google Scholar

  6. Marina Patysheva
    View author publications

    Search author on:PubMed Google Scholar

  7. Olga Cheremisina
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Jiri Barek.

Ethics declarations

All the volunteers gave written informed consent to participate in this investigation. The study was approved by Ethics Committee of Cancer Research Institute of Tomsk NRMC RAS and performed according to the guidelines of the Declaration of Helsinki.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Published in the topical collection Euroanalysis XX with guest editor Sibel A. Ozkan.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Popova, V., Korotkova, E., Barek, J. et al. Evaluation of human macrophage functional state by voltammetric monitoring of nitrite ions. Anal Bioanal Chem 412, 5097–5104 (2020). https://doi.org/10.1007/s00216-020-02399-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-020-02399-w

Keywords

Profiles

  1. Anton Fedorov View author profile
  2. Marina Patysheva View author profile