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Analysis of Nitrite and Nitrate in the Study of Inflammation

  • Claire A. Davies
  • Sophie A. Rocks
  • Meg C. O’ Shaughnessy
  • David Perrett
  • Paul G. Winyard
Part of the Methods in Molecular Biology book series (MIMB, volume 225)

Abstract

An acute inflammatory response is mounted in response to a stimulus such as tissue damage or the presence of an invading pathogen (1). If this stimulus cannot be removed, then chronic inflammation will develop as classically shown in rheumatoid arthritis (RA). Along with the array of cytokines and chemokines released during inflammation infiltrating macrophages and neutrophils release nitric oxide (NO), which is involved in killing the offending organism (2,3). Additionally, NO is known to mediate the inflammatory response by inhibiting or inducing inflammation via a variety of different pathways (4, 5, 6, 7, 8). For example, NO has been shown to activate and inhibit the transcription factor, nuclear factor-kappa B (NF-κB) (9). When NO activates NF-κB it induces the generation of proinflammatory cytokines such as tumor necrosis factor alpha (TNFα), which are thought to drive the chronic inflammatory response (10). However, NO can also cause the inhibition of NF-κB by upregulating the production of its inhibitor IκB (11,12). In a similar way, NO has been shown to inhibit neutrophil adhesion, preventing white blood cells (WBC) from infiltrating the site of inflammation (13). NO also increases the vascular permeability of the vessel wall so that WBCs can reach the affected tissue (14). The level of NO produced is thought to determine whether NO acts as a proinflammatory or antiinflammatory mediator. In many cases, the formation of peroxynitrite, from NO and superoxide, is thought to be responsible for some of the proinflammatory actions of NO (15).

Keywords

Electron Paramagnetic Resonance Fetal Calf Serum Xanthine Oxidase Solid Phase Extraction Cartridge Sterile Normal Saline 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Underwood, J. C. E. (1992) Pathology. 1st ed. Churchill Livingstone, Edinburgh.Google Scholar
  2. 2.
    Hibbs, Jr, J. B., Taintor, R. R., Vavrin, Z., Rachlin, E. M. (1988) Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem. Biophy. Res. Commun. 157, 87–94.CrossRefGoogle Scholar
  3. 3.
    Nathan, C. F. and Hibbs, Jr., J. B. (1991) Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr. Opin. Immunol. 3, 65–70.PubMedCrossRefGoogle Scholar
  4. 4.
    Frears, E. R., Zhang, Z., Blake, D. R., O’Connell, J. P., and Winyard, P. G. (1996) Inactivation of tissue inhibitor of metalloproteinase-1 by peroxynitrite. FEBS Lett. 381, 21–24.PubMedCrossRefGoogle Scholar
  5. 5.
    Rubbo, H., Parthasarathy, S., Barnes, S., Kirk, M., Kalyanaraman, B., and Freeman, B. A. (1995) Nitric oxide inhibition of lipoxygenase-dependent liposome and low-density lipoprotein oxidation: termination of radical chain propagation reactions and formation of nitrogen-containing oxidized lipid derivatives. Arch. Biochem. Biophys. 324, 15–25.PubMedCrossRefGoogle Scholar
  6. 6.
    Salvemini, D. and Masferrer, J. L. (1996) Interactions of nitric oxide with cyclooxygenase: in vitro, ex vivo, and in vivo studies. Methods Enzymol. 269, 12–25.PubMedCrossRefGoogle Scholar
  7. 7.
    Maccarrone, M., Corasaniti, M. T., Guerrieri, P., Nistico, G., and Finazzi, A.A. (1996) Nitric oxide-donor compounds inhibit lipoxygenase activity. Biochem. Biophys. Res. Commun. 219, 128–133.PubMedCrossRefGoogle Scholar
  8. 8.
    McInnes, I. B., Leung, B. P., Field, M., Wei, X. Q., Huang, F. P., Sturrock, R.D., et al. (1996) Production of nitric oxide in the synovial membrane of rheumatoid and osteoarthritis patients. J. Exp. Med. 184, 1519–1524.PubMedCrossRefGoogle Scholar
  9. 9.
    Connelly, L., Palacios-Callender, M., Ameixa, C., Moncada, S., and Hobbs, A. J. (2001) Biphasic regulation of NF-kappa B activity underlies the pro-and anti-inflammatory actions of nitric oxide. J. Immunol. 166, 3873–3881.PubMedGoogle Scholar
  10. 10.
    Kuo, H. P., Wang, C. H., Huang, K. S., Lin, H. C., Yu, C. T., Liu, C. Y., et al. (2000) Nitric oxide modulates interleukin-1beta and tumor necrosis factor-alpha synthesis by alveolar macrophages in pulmonary tuberculosis. Am. J. Respirat. Crit. Care Med. 161, 192–199.Google Scholar
  11. 11.
    Katsuyama, K., Shichiri, M., Marumo, F., and Hirata, Y. (1998) NO inhibits cytokine-induced iNOS expression and NF-kappaB activation by interfering with phosphorylation and degradation of I kappaB-alpha. Arterioscler. Thromb. Vas. Biol. 18, 1796–1802.Google Scholar
  12. 12.
    Peng, H. B., Libby, P., and Liao, J. K. (1995) Induction and stabilization of I kappa B alpha by nitric oxide mediates inhibition of NF-kappa B. J. Biol. Chem. 270, 14,214–14,219.PubMedCrossRefGoogle Scholar
  13. 13.
    Spiecker, M., Darius, H., Kaboth, K., Hubner, F., and Liao, J. K. (1998) Differential regulation of endothelial cell adhesion molecule expression by nitric oxide donors and antioxidants. J. Leuko. Biol. 63, 732–739.PubMedGoogle Scholar
  14. 14.
    Arnal, J. F., Dinh-Xuan, A. T., Pueyo, M., Darblade, B., and Rami, J. (1999) Endothelium-derived nitric oxide and vascular physiology and pathology. Cell Mol. Life Sci. 55, 1078–1087.PubMedCrossRefGoogle Scholar
  15. 15.
    Groves, J. T. (1999) Peroxynitrite: reactive, invasive and enigmatic. Curr. Opin. Chem. Biol. 3, 226–235.PubMedCrossRefGoogle Scholar
  16. 16.
    Feelisch, M. and Stamler, J. S. (1996) Methods in Nitric Oxide Research. Wiley, UK.Google Scholar
  17. 17.
    Vallance, P. and Chan, N. (2001) Endothelial function and nitric oxide: clinical relevance. Heart 85, 342–350.PubMedCrossRefGoogle Scholar
  18. 18.
    Prast, H. and Philippu, A. (2001) Nitric oxide as modulator of neuronal function. Progress Neurobiol. 64, 51–68.CrossRefGoogle Scholar
  19. 19.
    Zhang, Z., Naughton, D., Winyard, P. G., Benjamin, N., Blake, D. R., and Symons M. C. (1998) Generation of nitric oxide by a nitrite reductase activity of xanthine oxidase: a potential pathway for nitric oxide formation in the absence of nitric oxide synthase activity. Biochem. Biophys. Res. Commun. 249, 767–772.PubMedCrossRefGoogle Scholar
  20. 20.
    Millar, T. M., Stevens, C. R., Benjamin, N., Eisenthal, R., Harrison, R., and Blake, D. R. (1998) Xanthine oxidoreductase catalyses the reduction of nitrates and nitrite to nitric oxide under hypoxic conditions. FEBS Letts. 427, 225–228.CrossRefGoogle Scholar
  21. 21.
    Halliwell, B. and Gutteridge, J. M. C. (1999) Free radicals in biology and medicine. 3rd ed. Oxford University Press, Oxford.Google Scholar
  22. 22.
    Nazhat, N. B., Saadalla-Nazhat, R. A., Fairburn, K., Jones, P., Blake, D. R., Nielsen, B. R., et al. (1999) Nitrite determination in human plasma and synovial fluid using reation of nitric oxide with 3,5-dibromo-4-nitrosbenzene sulfonate (DBNBS). Biochim. Biophys. Acta 1427, 276–286.PubMedGoogle Scholar
  23. 23.
    Ueki, Y., Miyake, S., Tominaga, Y., and Eguchi, K. (1996) Increased nitric oxide levels in patients with rheumatoid arthritis. J. Rheumatol. 23, 230–236.PubMedGoogle Scholar
  24. 24.
    Farrell, A. J., Blake, D. R., Palmer, R. M., and Moncada, S. (1992) Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases. Ann. Rheum. Dis. 51, 1219–1222.PubMedCrossRefGoogle Scholar
  25. 25.
    Brundin L., Svenungsson E., Morcos E., Andersson M., Olsson T., Lundberg I., et al. (1998) Central nervous system nitric oxide formation in cerebral systemic lupus erythematosus. Ann. Neurol. 44, 704–706.PubMedCrossRefGoogle Scholar
  26. 26.
    Giovannoni, G., Land, J. M., Keir, G., Thompson, E. J., and Heales, S. J. (1997) Adaptation of the nitrate reductase and Griess reaction methods for the measurement of serum nitrate plus nitrite levels. Ann. Clin. Biochem. 34, 193–198.PubMedGoogle Scholar
  27. 27.
    El Menyawi, I., Looareesuwan, S., Knapp, S., Thalhammer, F., Stoiser, B., and Burgmann, H. (1998) Measurement of serum nitrite/nitrate concentrations using high-performance liquid chromatography. J. Chromatog. B., Biomed. Sci. Appl. 706, 347–351.CrossRefGoogle Scholar
  28. 28.
    Tsikas, D., Gutzki, F. M., Rossa, S., Bauer, H., Neumann, C., Dockendorff, K., et al. (1997) Measurement of nitrite and nitrate in biological fluids by gas chromatography-mass spectrometry and by the Griess assay: problems with the Griess assay-solutions by gas chromatography-mass spectrometry. Anal. Biochem. 244, 208–220.PubMedCrossRefGoogle Scholar
  29. 29.
    Chung, S. J. and Fung, H. L. (1992) Removal of ammonia interference in the redox chemiluminescence assay of nitric-oxide. Anal. Lett. 25, 2021–2036.Google Scholar
  30. 30.
    Davies, C. A., Perrett, D., Zhang, Z., Nielsen, B. R., Blake, D. R., and Winyard, P. G. (1999) Simultaneous analysis of nitrite, nitrate and the nicotinamide nucleotides by capillary electrophoresis: Application to biochemical studies and human extracellular fluids. Electrophoresis 20, 2111–2117.PubMedCrossRefGoogle Scholar
  31. 31.
    Moshage, H., Kok, B., Huizenga, J. R., and Jansen, P. L. (1995) Nitrite and nitrate determinations in plasma: a critical evaluation. Clin. Chem. 41, 892–896.PubMedGoogle Scholar
  32. 32.
    Hirano, T., Matsuda, T., Turner, M., Miyasaka, N., Buchan, G., Tang, B., et al. (1988) Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur. J. Immunol. 18, 1797–1801.PubMedCrossRefGoogle Scholar
  33. 33.
    Bergroth, V., Zvanifler, N. J., and Firestein, G. S. (1990) Cytokines in chronic inflammatory arthritis. III. Rheumatoid arthritis monocytes are not usually sensitive to γ-interferon, but have defective γ-interferon-mediated HA-DQ and HLA-DR induction. Arthr. Rheum. 32, 1074–1079.CrossRefGoogle Scholar
  34. 34.
    Firestein, G. S., Alvaro-Gracia, J. M., and Maki, M. (1990) Quantitative analysis of cytokine gene expression in rheumatoid arthritis. J Immunol. 144, 3347–3353.PubMedGoogle Scholar
  35. 35.
    Sakurai, H., Kohsaka, H., Liu, M. F, Higashiyama, H., Hirata, Y., Kanno, K., et al. (1995) Nitric oxide production and inducible nitric oxide synthase expression in inflammatory arthritis. J. Clin. Invest. 96, 2357–2363.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2003

Authors and Affiliations

  • Claire A. Davies
    • 1
  • Sophie A. Rocks
    • 1
  • Meg C. O’ Shaughnessy
    • 1
  • David Perrett
    • 2
  • Paul G. Winyard
    • 3
  1. 1.The William Harvey Research InstituteLondonUK
  2. 2.Barts and The London School of Medicine and DentistryLondonUK
  3. 3.Peninsula Medical SchoolUniversities of Exeter and PlymouthExeterUK

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