Taurine 7 pp 463-472 | Cite as

Production of Reactive Oxygen and Nitrogen Species in Phagocytes is Regulated by Taurine Chloramine

  • Chaekyun Kim
  • Young-Nam Cha
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 643)


Taurine is abundantly present in phagocytic cells and provides protection against cytotoxicity caused by reactive oxygen species (ROS). The reaction between taurine and HOCl, a toxic product of the myeloperoxidase (MPO) system, generates a more stable and less toxic product, taurine chloramine (TauCl). TauCl has also been shown to inhibit the production of superoxide anion (O2 -) and nitric oxide (NO). In this review, we compare the effect of taurine and TauCl on the production of these reactive species in phagocytes. First, TauCl inhibit PMA-derived O2 - production and this is associated with inhibition of p47phox phosphorylation and of p47phox and p67phox translocation. Second, TauCl inhibits LPS-induced iNOS expression and NO production. This occurs by direct inhibition of Ras activation, ERK1/2 phosphorylation and NF-κB activation. Third, TauCl by itself increases the expression of heme oxygenase-1 (HO-1) and enhances HO activity. Carbon monoxide (CO), a product of HO activity, is able to inhibit both O2 - and NO production. Combined, these effects of TauCl appear to provide cytoprotection against the inadvertent cytotoxicity caused by overproduction of O2 - and NO.


Nitric Oxide iNOS Expression Heme Oxygenase Activity Taurine Chloramine Gaseous Signal Molecule 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ajizian SJ, English BK, Meals EA (1999) Specific inhibitors of p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways block inducible nitric oxide synthase and tumor necrosis factor accumulation in murine macrophages stimulated with lipopolysaccharide and interferon-gamma. J Infect Dis 179(4):939–944PubMedCrossRefGoogle Scholar
  2. Babior BM (1999) NADPH oxidase: an update. Blood 93(5):1464–1476PubMedGoogle Scholar
  3. Baron DN (1969) Down with plasma. Intracellular chemical pathology studied by analysis of cells of solid tissues, erythrocytes, and leukocytes. Proc R Soc Med 62(9):945–953PubMedGoogle Scholar
  4. Barua M, Liu Y, Quinn MR (2001) Taurine chloramine inhibits inducible nitric oxide synthase and TNF-alpha gene expression in activated alveolar macrophages: decreased NF-kappaB activation and IkappaB kinase activity. J Immunol 167(4):2275–2281PubMedGoogle Scholar
  5. Bhat NR, Zhang P, Lee JC, Hogan EL (1998) Extracellular signal-regulated kinase and p38 subgroups of mitogen-activated protein kinases regulate inducible nitric oxide synthase and tumor necrosis factor-alpha gene expression in endotoxin-stimulated primary glial cultures. J Neurosci 18(5):1633–1641PubMedGoogle Scholar
  6. Buscher D, Hipskind RA, Krautwald S, Reimann T, Baccarini M (1995) Ras-dependent and -independent pathways target the mitogen-activated protein kinase network in macrophages. Mol Cell Biol 15(1):466–475PubMedGoogle Scholar
  7. Choi HS, Cha YN, Kim C (2006) Taurine chloramine inhibits PMA-stimulated superoxide production in human neutrophils perhaps by inhibiting phosphorylation and translocation of p47(phox). Int Immunopharmacol 6(9):1431–1440PubMedCrossRefGoogle Scholar
  8. Dinauer MC (2003) Regulation of neutrophil function by Rac GTPases. Curr Opin Hematol 10(1):8–15PubMedCrossRefGoogle Scholar
  9. Fukuda K, Hirai Y, Yoshida H, Nakajima T, Usui T (1982) Free amino acid content of lymphocytes and granulocytes compared. Clin Chem 28(8):1758–1761PubMedGoogle Scholar
  10. Grisham MB, Jefferson MM, Thomas EL (1984) Role of monochloramine in the oxidation of erythrocyte hemoglobin by stimulated neutrophils. J Biol Chem 259(11):6757–6765PubMedGoogle Scholar
  11. Groemping Y, Rittinger K (2005) Activation and assembly of the NADPH oxidase: a structural perspective. Biochem J 386(Pt 3):401–416PubMedGoogle Scholar
  12. Huie RE, Padmaja S (1993) The reaction of no with superoxide. Free Radic Res Commun 18(4):195–199PubMedCrossRefGoogle Scholar
  13. Huxtable RJ (1992) Physiological actions of taurine. Physiol Rev 72(1):101–163.PubMedGoogle Scholar
  14. Ignarro LJ (1996) Physiology and pathophysiology of nitric oxide. Kidney Int Suppl 55:S2–S5PubMedGoogle Scholar
  15. Kanayama A, Inoue J, Sugita-Konishi Y, Shimizu M, Miyamoto Y (2002) Oxidation of Ikappa Balpha at methionine 45 is one cause of taurine chloramine-induced inhibition of NF-kappa B activation. J Biol Chem 277(27):24049–24056PubMedCrossRefGoogle Scholar
  16. Kim C, Chung JK, Jeong JM, Chang YS, Lee YJ, Kim YJ, Lee MC, Koh CS, Kim BK (1998) Uptake of taurine and taurine chloramine in murine macrophages and their distribution in mice with experimental inflammation. Adv Exp Med Biol 442:169–176PubMedGoogle Scholar
  17. Kim C, Park E, Quinn MR, Schuller-Levis G (1996) The production of superoxide anion and nitric oxide by cultured murine leukocytes and the accumulation of TNF-alpha in the conditioned media is inhibited by taurine chloramine. Immunopharmacology 34(2–3):89–95PubMedCrossRefGoogle Scholar
  18. Kim JW, Kim C (2005) Inhibition of LPS-induced NO production by taurine chloramine in macrophages is mediated though Ras-ERK-NF-kappaB. Biochem Pharmacol 70(9):1352–1360PubMedCrossRefGoogle Scholar
  19. Kim KS, Park EK, Ju SM, Jung HS, Bang JS, Kim C, Lee YA, Hong SJ, Lee SH, Yang HI, Yoo MC (2007) Taurine chloramine differentially inhibits matrix metalloproteinase 1 and 13 synthesis in interleukin-1beta stimulated fibroblast-like synoviocytes. Arthritis Res Ther 9(4):R80PubMedCrossRefGoogle Scholar
  20. Kontny E, Maslinski W, Marcinkiewicz J (2003a) Anti-inflammatory activities of taurine chloramine: implication for immunoregulation and pathogenesis of rheumatoid arthritis. Adv Exp Med Biol 526:329–340Google Scholar
  21. Kontny E, Rudnicka W, Kowalczewski J, Marcinkiewicz J, Maslinski W (2003b) Selective inhibition of cyclooxygenase 2-generated prostaglandin E2 synthesis in rheumatoid arthritis synoviocytes by taurine chloramine. Arthritis Rheum 48(6):1551–1555CrossRefGoogle Scholar
  22. Kuribayashi F, Nunoi H, Wakamatsu K, Tsunawaki S, Sato K, Ito T, Sumimoto H (2002) The adaptor protein p40(phox) as a positive regulator of the superoxide-producing phagocyte oxidase. Embo J 21(23):6312–6320PubMedCrossRefGoogle Scholar
  23. Learn DB, Fried VA, Thomas EL (1990) Taurine and hypotaurine content of human leukocytes. J Leukoc Biol 48(2):174–182PubMedGoogle Scholar
  24. Lopes LR, Dagher MC, Gutierrez A, Young B, Bouin AP, Fuchs A, Babior BM (2004) Phosphorylated p40PHOX as a negative regulator of NADPH oxidase. Biochemistry 43(12):3723–3730PubMedCrossRefGoogle Scholar
  25. Marcinkiewicz J, Grabowska A, Bereta J, Stelmaszynska T (1995) Taurine chloramine, a product of activated neutrophils, inhibits in vitro the generation of nitric oxide and other macrophage inflammatory mediators. J Leukoc Biol 58(6):667–674PubMedGoogle Scholar
  26. Marquez LA, Dunford HB (1994) Chlorination of taurine by myeloperoxidase. Kinetic evidence for an enzyme-bound intermediate. J Biol Chem 269(11):7950–7956PubMedGoogle Scholar
  27. Midwinter RG, Peskin AV, Vissers MC, Winterbourn CC (2004) Extracellular oxidation by taurine chloramine activates ERK via the epidermal growth factor receptor. J Biol Chem 279(31):32205–32211PubMedCrossRefGoogle Scholar
  28. Motterlini R, Green CJ, Foresti R (2002) Regulation of heme oxygenase-1 by redox signals involving nitric oxide. Antioxid Redox Signal 4(4):615–624PubMedCrossRefGoogle Scholar
  29. Nauseef WM (2004) Assembly of the phagocyte NADPH oxidase. Histochem Cell Biol 122(4):277–291PubMedCrossRefGoogle Scholar
  30. Ogino T, Kobuchi H, Sen CK, Roy S, Packer L, Maguire JJ (1997) Monochloramine inhibits phorbol ester-inducible neutrophil respiratory burst activation and T cell interleukin-2 receptor expression by inhibiting inducible protein kinase C activity. J Biol Chem 272(42):26247–26252PubMedCrossRefGoogle Scholar
  31. Olszanecki R, Marcinkiewicz J (2004) Taurine chloramine and taurine bromamine induce heme oxygenase-1 in resting and LPS-stimulated J774.2 macrophages. Amino Acids 27(1):29–35PubMedCrossRefGoogle Scholar
  32. Otterbein LE, Bach FH, Alam J, Soares M, Tao Lu H, Wysk M, Davis RJ, Flavell RA, Choi AM (2000) Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 6(4):422–428PubMedCrossRefGoogle Scholar
  33. Park E, Alberti J, Quinn MR, Schuller-Levis G (1998) Taurine chloramine inhibits the production of superoxide anion, IL-6 and IL-8 in activated human polymorphonuclear leukocytes. Adv Exp Med Biol 442:177–182PubMedGoogle Scholar
  34. Park E, Jia J, Quinn MR, Schuller-Levis G (2002) Taurine chloramine inhibits lymphocyte proliferation and decreases cytokine production in activated human leukocytes. Clin Immunol 102(2):179–184PubMedCrossRefGoogle Scholar
  35. Park E, Quinn MR, Wright CE, Schuller-Levis G (1993) Taurine chloramine inhibits the synthesis of nitric oxide and the release of tumor necrosis factor in activated RAW 264.7 cells. J Leukoc Biol 54(2):119–124PubMedGoogle Scholar
  36. Park E, Schuller-Levis G, Quinn MR (1995) Taurine chloramine inhibits production of nitric oxide and TNF-alpha in activated RAW 264.7 cells by mechanisms that involve transcriptional and translational events. J Immunol 154(9):4778–4784PubMedGoogle Scholar
  37. Pero RW, Sheng Y, Olsson A, Bryngelsson C, Lund-Pero M (1996) Hypochlorous acid/ N-chloramines are naturally produced DNA repair inhibitors. Carcinogenesis 17(1):13–18PubMedCrossRefGoogle Scholar
  38. Petrache I, Otterbein LE, Alam J, Wiegand GW, Choi AM (2000) Heme oxygenase-1 inhibits TNF-alpha-induced apoptosis in cultured fibroblasts. Am J Physiol Lung Cell Mol Physiol 278(2):L312–L319PubMedGoogle Scholar
  39. Schuller-Levis GB, Park E (2003) Taurine: new implications for an old amino acid. FEMS Microbiol Lett 226(2):195–202PubMedCrossRefGoogle Scholar
  40. Srisook K, Cha YN (2004) Biphasic induction of heme oxygenase-1 expression in macrophages stimulated with lipopolysaccharide. Biochem Pharmacol 68(9):1709–1720PubMedCrossRefGoogle Scholar
  41. Srisook K, Han SS, Choi HS, Li MH, Ueda H, Kim C, Cha YN (2006) CO from enhanced HO activity or from CORM-2 inhibits both O2- and NO production and downregulates HO-1 expression in LPS-stimulated macrophages. Biochem Pharmacol 71(3):307–318PubMedCrossRefGoogle Scholar
  42. Tallan HH, Jacobson E, Wright CE, Schneidman K, Gaull GE (1983) Taurine uptake by cultured human lymphoblastoid cells. Life Sci 33(19):1853–1860PubMedCrossRefGoogle Scholar
  43. Tenhunen R, Marver HS, Schmid R (1968) The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci USA 61(2):748–755PubMedCrossRefGoogle Scholar
  44. Thomas EL, Grisham MB, Melton DF, Jefferson MM (1985) Evidence for a role of taurine in the in vitro oxidative toxicity of neutrophils toward erythrocytes. J Biol Chem 260(6):3321–3329PubMedGoogle Scholar
  45. Vinton NE, Laidlaw SA, Ament ME, Kopple JD (1986) Taurine concentrations in plasma and blood cells of patients undergoing long-term parenteral nutrition. Am J Clin Nutr 44(3):398–404PubMedGoogle Scholar
  46. Watters JJ, Sommer JA, Pfeiffer ZA, Prabhu U, Guerra AN, Bertics PJ (2002) A differential role for the mitogen-activated protein kinases in lipopolysaccharide signaling: the MEK/ERK pathway is not essential for nitric oxide and interleukin 1beta production. J Biol Chem 277(11): 9077–9087PubMedCrossRefGoogle Scholar
  47. Witko V, Nguyen AT, Descamps-Latscha B (1992) Microtiter plate assay for phagocyte-derived taurine-chloramines. J Clin Lab Anal 6(1):47–53PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Chaekyun Kim
    • 1
  • Young-Nam Cha
  1. 1.Laboratory for Leukocyte Signaling Research and Center for Advanced Medical Education by BK21 ProjectIncheonKorea

Personalised recommendations