Immunologic Research

, Volume 43, Issue 1–3, pp 198–209

Redox warfare between airway epithelial cells and Pseudomonas: dual oxidase versus pyocyanin

Article

Abstract

The importance of reactive oxygen species-dependent microbial killing by the phagocytic cell NADPH oxidase has been appreciated for some time, although only recently has an appreciation developed for the partnership of lactoperoxidase with related dual oxidases (Duox) within secretions of the airway surface layer. This system produces mild oxidants designed for extracellular killing that are effective against several airway pathogens, including Staphylococcus aureus, Burkholderia cepacia, and Pseudomonas aeruginosa. Establishment of chronic pseudomonas infections involves adaptations to resist oxidant-dependent killing by expression of a redox-active virulence factor, pyocyanin, that competitively inhibits epithelial Duox activity by consuming intracellular NADPH and producing superoxide, thereby inflicting oxidative stress on the host.

Keywords

NADPH oxidase Nox Dual oxidase Pyocyanin Pseudomonas aeruginosa Cystic fibrosis Airway epithelium Hydrogen peroxide Oxidative stress 

References

  1. 1.
    Leto TL. The respiratory burst oxidase. In: Gallin JI, Snyderman R, editors. Inflammation. Basic principles and clinical correlates. Philadelphia: Lippincott Williams and Wilkins; 1999. p. 769–86.Google Scholar
  2. 2.
    Segal BH, Leto TL, Gallin JI, Malech HL, Holland SM. Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore). 2000;79:170–200.CrossRefGoogle Scholar
  3. 3.
    Finkel T. Reactive oxygen species and signal transduction. IUBMB Life. 2001;52:3–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Geiszt M, Leto TL. The Nox family of NAD(P)H oxidases: host defense and beyond. J Biol Chem. 2004;279:51715–18.PubMedCrossRefGoogle Scholar
  5. 5.
    Lambeth JD. NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol. 2004;4:181–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Nauseef WM. Biological roles for the NOX family NADPH oxidases. J Biol Chem. 2008;283:16961–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Rada B, Leto TL. Oxidative innate immune defenses by Nox/Duox family NADPH oxidases. Contrib Microbiol. 2008;15:164–87.PubMedCrossRefGoogle Scholar
  8. 8.
    Leto TL, Geiszt M. Role of Nox family NADPH oxidases in host defense. Antioxid Redox Signal. 2006;8:1549–61.PubMedCrossRefGoogle Scholar
  9. 9.
    Geiszt M, Lekstrom K, Brenner S, Hewitt SM, Dana R, Malech HL, et al. NAD(P)H oxidase 1, a product of differentiated colon epithelial cells, can partially replace glycoprotein 91phox in the regulated production of superoxide by phagocytes. J Immunol. 2003;171:299–306.PubMedGoogle Scholar
  10. 10.
    Harper RW, Xu C, Eiserich JP, Chen Y, Kao CY, Thai P, et al. Differential regulation of dual NADPH oxidases/peroxidases, Duox1 and Duox2, by Th1 and Th2 cytokines in respiratory tract epithelium. FEBS Lett. 2005;579:4911–17.PubMedCrossRefGoogle Scholar
  11. 11.
    Sturrock A, Huecksteadt TP, Norman K, Sanders K, Murphy TM, Chitano P, et al. Nox4 mediates TGF-beta1-induced retinoblastoma protein phosphorylation, proliferation, and hypertrophy in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2007;292:L1543–55.PubMedCrossRefGoogle Scholar
  12. 12.
    Sturrock A, Cahill B, Norman K, Huecksteadt TP, Hill K, Sanders K, et al. Transforming growth factor-beta1 induces Nox4 NAD(P)H oxidase and reactive oxygen species-dependent proliferation in human pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2006;290:L661–73.PubMedCrossRefGoogle Scholar
  13. 13.
    Kawahara T, Kuwano Y, Teshima-Kondo S, Takeya R, Sumimoto H, Kishi K, et al. Role of nicotinamide adenine dinucleotide phosphate oxidase 1 in oxidative burst response to Toll-like receptor 5 signaling in large intestinal epithelial cells. J Immunol. 2004;172:3051–8.PubMedGoogle Scholar
  14. 14.
    Kawahara T, Kohjima M, Kuwano Y, Mino H, Teshima-Kondo S, Takeya R, et al. Helicobacter pylori lipopolysaccharide activates Rac1 and transcription of NADPH oxidase Nox1 and its organizer NOXO1 in guinea pig gastric mucosal cells. Am J Physiol Cell Physiol. 2005;288:C450–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Park HS, Jung HY, Park EY, Kim J, Lee WJ, Bae YS. Cutting edge: direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NF-kappa B. J Immunol. 2004;173:3589–93.PubMedGoogle Scholar
  16. 16.
    Geiszt M, Witta J, Baffi J, Lekstrom K, Leto TL. Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense. FASEB J. 2003;17:1502–4.PubMedGoogle Scholar
  17. 17.
    Reiter B, Marshall VM, Bjorck L, Rosen CG. Nonspecific bactericidal activity of the lactoperoxidases-thiocyanate-hydrogen peroxide system of milk against Escherichia coli and some gram-negative pathogens. Infect Immun. 1976;13:800–7.PubMedGoogle Scholar
  18. 18.
    Pruitt KM. The salivary peroxidase system: thermodynamic, kinetic and antibacterial properties. J Oral Pathol. 1987;16:417–20.PubMedGoogle Scholar
  19. 19.
    Wijkstrom-Frei C, El-Chemaly S, Ali-Rachedi R, Gerson C, Cobas MA, Forteza R, et al. Lactoperoxidase and human airway host defense. Am J Respir Cell Mol Biol. 2003;29:206–12.PubMedCrossRefGoogle Scholar
  20. 20.
    Ratner AJ, Prince A. Lactoperoxidase. New recognition of an “old” enzyme in airway defenses. Am J Respir Cell Mol Biol. 2000;22:642–4.PubMedGoogle Scholar
  21. 21.
    Nauseef WM. Assembly of the phagocyte NADPH oxidase. Histochem Cell Biol. 2004;122:277–91.PubMedCrossRefGoogle Scholar
  22. 22.
    Ueyama T, Kusakabe T, Karasawa S, Kawasaki T, Shimizu A, Son J, et al. Sequential binding of cytosolic Phox complex to phagosomes through regulated adaptor proteins: evaluation using the novel monomeric Kusabira-Green System and live imaging of phagocytosis. J Immunol. 2008;181:629–40.PubMedGoogle Scholar
  23. 23.
    Grasberger H, Refetoff S. Identification of the maturation factor for dual oxidase. Evolution of an eukaryotic operon equivalent. J Biol Chem. 2006;281:18269–72.PubMedCrossRefGoogle Scholar
  24. 24.
    Forteza R, Salathe M, Miot F, Conner GE. Regulated hydrogen peroxide production by Duox in human airway epithelial cells. Am J Respir Cell Mol Biol. 2005;32:462–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Ameziane-El Hassani R, Morand S, Boucher JL, Frapart YM, Apostolou D, Agnandji D, et al. Duox2 has intrinsic Ca2+-dependent H2O2-generating activity. J Biol Chem. 2005;280:30046–54.PubMedCrossRefGoogle Scholar
  26. 26.
    Banfi B, Tirone F, Durussel I, Knisz J, Moskwa P, Molnar GZ, et al. Mechanism of Ca2+ activation of the NADPH oxidase 5 (NOX5). J Biol Chem. 2004;279:18583–91.PubMedCrossRefGoogle Scholar
  27. 27.
    Edens WA, Sharling L, Cheng G, Shapira R, Kinkade JM, Lee T, et al. Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91phox. J Cell Biol. 2001;154:879–91.PubMedCrossRefGoogle Scholar
  28. 28.
    Bjorck L, Rosen C, Marshall V, Reiter B. Antibacterial activity of the lactoperoxidase system in milk against pseudomonads and other gram-negative bacteria. Appl Microbiol. 1975;30:199–204.PubMedGoogle Scholar
  29. 29.
    Johansen C, Falholt P, Gram L. Enzymatic removal and disinfection of bacterial biofilms. Appl Environ Microbiol. 1997;63:3724–8.PubMedGoogle Scholar
  30. 30.
    Oram JD, Reiter B. The inhibition of streptococci by lactoperoxidase, thiocyanate and hydrogen peroxide. The oxidation of thiocyanate and the nature of the inhibitory compound. Biochem J. 1966;100:382–8.PubMedGoogle Scholar
  31. 31.
    Oram JD, Reiter B. The inhibition of streptococci by lactoperoxidase, thiocyanate and hydrogen peroxide. The effect of the inhibitory system on susceptible and resistant strains of group N streptococci. Biochem J. 1966;100:373–81.PubMedGoogle Scholar
  32. 32.
    Thomas EL, Milligan TW, Joyner RE, Jefferson MM. Antibacterial activity of hydrogen peroxide and the lactoperoxidase-hydrogen peroxide-thiocyanate system against oral streptococci. Infect Immun. 1994;62:529–35.PubMedGoogle Scholar
  33. 33.
    Thomas EL, Pera KA, Smith KW, Chwang AK. Inhibition of Streptococcus mutans by the lactoperoxidase antimicrobial system. Infect Immun. 1983;39:767–78.PubMedGoogle Scholar
  34. 34.
    Courtois P, van Beers D, de Foor M, Mandelbaum IM, Pourtois M. Abolition of herpes simplex cytopathic effect after treatment with peroxidase generated hypothiocyanite. J Biol Buccale. 1990;18:71–4.PubMedGoogle Scholar
  35. 35.
    Pourtois M, Binet C, Van Tieghem N, Courtois P, Vandenabbeele A, Thiry L. Inhibition of HIV infectivity by lactoperoxidase-produced hypothiocyanite. J Biol Buccale. 1990;18:251–3.PubMedGoogle Scholar
  36. 36.
    Lenander-Lumikari M. Inhibition of Candida albicans by the peroxidase/SCN/H2O2 system. Oral Microbiol Immunol. 1992;7:315–20.PubMedCrossRefGoogle Scholar
  37. 37.
    Popper L, Knorr D. Inactivation of yeast and filamentous fungi by the lactoperoxidase-hydrogen peroxide-thiocyanate-system. Nahrung. 1997;41:29–33.PubMedCrossRefGoogle Scholar
  38. 38.
    Paul BD, Smith ML. Cyanide and thiocyanate in human saliva by gas chromatography-mass spectrometry. J Anal Toxicol. 2006;30:511–15.PubMedGoogle Scholar
  39. 39.
    Jalil RA. Concentrations of thiocyanate and hypothiocyanite in the saliva of young adults. J Nihon Univ Sch Dent. 1994;36:254–60.PubMedGoogle Scholar
  40. 40.
    Ferreira IM, Hazari MS, Gutierrez C, Zamel N, Chapman KR. Exhaled nitric oxide and hydrogen peroxide in patients with chronic obstructive pulmonary disease: effects of inhaled beclomethasone. Am J Respir Crit Care Med. 2001;164:1012–15.PubMedGoogle Scholar
  41. 41.
    van Dalen CJ, Whitehouse MW, Winterbourn CC, Kettle AJ. Thiocyanate and chloride as competing substrates for myeloperoxidase. Biochem J. 1997;327(Pt 2):487–92.PubMedGoogle Scholar
  42. 42.
    Ashby MT, Carlson AC, Scott MJ. Redox buffering of hypochlorous acid by thiocyanate in physiologic fluids. J Am Chem Soc. 2004;126:15976–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Linsdell P, Hanrahan JW. Adenosine triphosphate-dependent asymmetry of anion permeation in the cystic fibrosis transmembrane conductance regulator chloride channel. J Gen Physiol. 1998;111:601–14.PubMedCrossRefGoogle Scholar
  44. 44.
    Illek B, Tam AW, Fischer H, Machen TE. Anion selectivity of apical membrane conductance of Calu 3 human airway epithelium. Pflugers Arch. 1999;437:812–22.PubMedCrossRefGoogle Scholar
  45. 45.
    Moskwa P, Lorentzen D, Excoffon KJ, Zabner J, McCray PB Jr, Nauseef WM, et al. A novel host defense system of airways is defective in cystic fibrosis. Am J Respir Crit Care Med. 2007;175:174–83.PubMedCrossRefGoogle Scholar
  46. 46.
    Conner GE, Wijkstrom-Frei C, Randell SH, Fernandez VE, Salathe M. The lactoperoxidase system links anion transport to host defense in cystic fibrosis. FEBS Lett. 2007;581:271–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Rada B, Lekstrom K, Damian S, Dupuy C, Leto TL. The pseudomonas toxin pyocyanin inhibits the dual oxidase-based antimicrobial system as it imposes oxidative stress on airway epithelial cells. J Immunol. 2008;181:4883–93.PubMedGoogle Scholar
  48. 48.
    Pedemonte N, Caci E, Sondo E, Caputo A, Rhoden K, Pfeffer U, et al. Thiocyanate transport in resting and IL-4-stimulated human bronchial epithelial cells: role of pendrin and anion channels. J Immunol. 2007;178:5144–53.PubMedGoogle Scholar
  49. 49.
    Caputo A, Caci E, Ferrera L, Pedemonte N, Barsanti C, Sondo E, Pfeffer U, Ravazzolo R, Zegarra-Moran O, Galietta LJ. TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity. Science. 2008; PMID: 18772398.Google Scholar
  50. 50.
    Campodonico VL, Gadjeva M, Paradis-Bleau C, Uluer A, Pier GB. Airway epithelial control of Pseudomonas aeruginosa infection in cystic fibrosis. Trends Mol Med. 2008;14:120–33.PubMedGoogle Scholar
  51. 51.
    Lau GW, Hassett DJ, Britigan BE. Modulation of lung epithelial functions by Pseudomonas aeruginosa. Trends Microbiol. 2005;13:389–97.PubMedCrossRefGoogle Scholar
  52. 52.
    Price-Whelan A, Dietrich LE, Newman DK. Rethinking ‘secondary’ metabolism: physiological roles for phenazine antibiotics. Nat Chem Biol. 2006;2:71–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Wilson R, Sykes DA, Watson D, Rutman A, Taylor GW, Cole PJ. Measurement of Pseudomonas aeruginosa phenazine pigments in sputum and assessment of their contribution to sputum sol toxicity for respiratory epithelium. Infect Immun. 1988;56:2515–17.PubMedGoogle Scholar
  54. 54.
    Dietrich LE, Teal TK, Price-Whelan A, Newman DK. Redox-active antibiotics control gene expression and community behavior in divergent bacteria. Science. 2008;321:1203–6.PubMedCrossRefGoogle Scholar
  55. 55.
    Lau GW, Hassett DJ, Ran H, Kong F. The role of pyocyanin in Pseudomonas aeruginosa infection. Trends Mol Med. 2004;10:599–606.PubMedCrossRefGoogle Scholar
  56. 56.
    O’Malley YQ, Reszka KJ, Spitz DR, Denning GM, Britigan BE. Pseudomonas aeruginosa pyocyanin directly oxidizes glutathione and decreases its levels in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2004;287:L94–103.PubMedCrossRefGoogle Scholar
  57. 57.
    Muller PK, Krohn K, Muhlradt PF. Effects of pyocyanine, a phenazine dye from Pseudomonas aeruginosa, on oxidative burst and bacterial killing in human neutrophils. Infect Immun. 1989;57:2591–6.PubMedGoogle Scholar
  58. 58.
    Reszka KJ, O’Malley Y, McCormick ML, Denning GM, Britigan BE. Oxidation of pyocyanin, a cytotoxic product from Pseudomonas aeruginosa, by microperoxidase 11 and hydrogen peroxide. Free Radic Biol Med. 2004;36:1448–59.PubMedCrossRefGoogle Scholar
  59. 59.
    Schwarzer C, Machen TE, Illek B, Fischer H. NADPH oxidase-dependent acid production in airway epithelial cells. J Biol Chem. 2004;279:36454–61.PubMedCrossRefGoogle Scholar
  60. 60.
    Shao MX, Nadel JA. Dual oxidase 1-dependent MUC5AC mucin expression in cultured human airway epithelial cells. Proc Natl Acad Sci USA. 2005;102:767–72.PubMedCrossRefGoogle Scholar
  61. 61.
    Wesley UV, Bove PF, Hristova M, McCarthy S, van der Vliet A. Airway epithelial cell migration and wound repair by ATP-mediated activation of dual oxidase 1. J Biol Chem. 2007;282:3213–20.PubMedCrossRefGoogle Scholar
  62. 62.
    Look DC, Stoll LL, Romig SA, Humlicek A, Britigan BE, Denning GM. Pyocyanin and its precursor phenazine-1-carboxylic acid increase IL-8 and intercellular adhesion molecule-1 expression in human airway epithelial cells by oxidant-dependent mechanisms. J Immunol. 2005;175:4017–23.PubMedGoogle Scholar
  63. 63.
    Denning GM, Wollenweber LA, Railsback MA, Cox CD, Stoll LL, Britigan BE. Pseudomonas pyocyanin increases interleukin-8 expression by human airway epithelial cells. Infect Immun. 1998;66:5777–84.PubMedGoogle Scholar
  64. 64.
    Usher LR, Lawson RA, Geary I, Taylor CJ, Bingle CD, Taylor GW, et al. Induction of neutrophil apoptosis by the Pseudomonas aeruginosa exotoxin pyocyanin: a potential mechanism of persistent infection. J Immunol. 2002;168:1861–8.PubMedGoogle Scholar
  65. 65.
    Allen L, Dockrell DH, Pattery T, Lee DG, Cornelis P, Hellewell PG, et al. Pyocyanin production by Pseudomonas aeruginosa induces neutrophil apoptosis and impairs neutrophil-mediated host defenses in vivo. J Immunol. 2005;174:3643–9.PubMedGoogle Scholar
  66. 66.
    Bianchi SM, Prince LR, McPhillips K, Allen L, Marriott HM, Taylor GW, et al. Impairment of apoptotic cell engulfment by pyocyanin, a toxic metabolite of Pseudomonas aeruginosa. Am J Respir Crit Care Med. 2008;177:35–43.PubMedCrossRefGoogle Scholar
  67. 67.
    Kanthakumar K, Cundell DR, Johnson M, Wills PJ, Taylor GW, Cole PJ, et al. Effect of salmeterol on human nasal epithelial cell ciliary beating: inhibition of the ciliotoxin, pyocyanin. Br J Pharmacol. 1994;112:493–8.PubMedGoogle Scholar
  68. 68.
    Munro NC, Barker A, Rutman A, Taylor G, Watson D, McDonald-Gibson WJ, et al. Effect of pyocyanin and 1-hydroxyphenazine on in vivo tracheal mucus velocity. J Appl Physiol. 1989;67:316–23.PubMedGoogle Scholar
  69. 69.
    Dormehl I, Ras G, Taylor G, Hugo N. Effect of Pseudomonas aeruginosa-derived pyocyanin and 1-hydroxyphenazine on pulmonary mucociliary clearance monitored scintigraphically in the baboon model. Int J Rad Appl Instrum B. 1991;18:455–9.PubMedGoogle Scholar
  70. 70.
    Ran H, Hassett DJ, Lau GW. Human targets of Pseudomonas aeruginosa pyocyanin. Proc Natl Acad Sci USA. 2003;100:14315–20.PubMedCrossRefGoogle Scholar
  71. 71.
    Kong F, Young L, Chen Y, Ran H, Meyers M, Joseph P, et al. Pseudomonas aeruginosa pyocyanin inactivates lung epithelial vacuolar ATPase-dependent cystic fibrosis transmembrane conductance regulator expression and localization. Cell Microbiol. 2006;8:1121–33.PubMedCrossRefGoogle Scholar
  72. 72.
    Schwarzer C, Fu Z, Fischer H, Machen TE. Redox-independent activation of NF-kB by P. aeruginosa pyocyanin in a CF airway epithelial cell line. J Biol Chem. 2008;283:27144–53.PubMedCrossRefGoogle Scholar
  73. 73.
    Schwarzer C, Fischer H, Kim EJ, Barber KJ, Mills AD, Kurth MJ, et al. Oxidative stress caused by pyocyanin impairs CFTR Cl(-) transport in human bronchial epithelial cells. Free Radic Biol Med. 2008; PMID: 18845244.Google Scholar
  74. 74.
    O’Malley YQ, Abdalla MY, McCormick ML, Reszka KJ, Denning GM, Britigan BE. Subcellular localization of Pseudomonas pyocyanin cytotoxicity in human lung epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2003;284:L420–30.PubMedGoogle Scholar
  75. 75.
    Muller M. Premature cellular senescence induced by pyocyanin, a redox-active Pseudomonas aeruginosa toxin. Free Radic Biol Med. 2006;41:1670–7.PubMedCrossRefGoogle Scholar
  76. 76.
    Denning GM, Railsback MA, Rasmussen GT, Cox CD, Britigan BE. Pseudomonas pyocyanine alters calcium signaling in human airway epithelial cells. Am J Physiol. 1998;274:L893–900.PubMedGoogle Scholar
  77. 77.
    O’Malley YQ, Reszka KJ, Rasmussen GT, Abdalla MY, Denning GM, Britigan BE. The Pseudomonas secretory product pyocyanin inhibits catalase activity in human lung epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2003;285:L1077–86.PubMedGoogle Scholar
  78. 78.
    Britigan BE, Railsback MA, Cox CD. The Pseudomonas aeruginosa secretory product pyocyanin inactivates alpha1 protease inhibitor: implications for the pathogenesis of cystic fibrosis lung disease. Infect Immun. 1999;67:1207–12.PubMedGoogle Scholar
  79. 79.
    Shellito J, Nelson S, Sorensen RU. Effect of pyocyanine, a pigment of Pseudomonas aeruginosa, on production of reactive nitrogen intermediates by murine alveolar macrophages. Infect Immun. 1992;60:3913–5.PubMedGoogle Scholar
  80. 80.
    Lauredo IT, Sabater JR, Ahmed A, Botvinnikova Y, Abraham WM. Mechanism of pyocyanin- and 1-hydroxyphenazine-induced lung neutrophilia in sheep airways. J Appl Physiol. 1998;85:2298–304.PubMedGoogle Scholar
  81. 81.
    Ulmer AJ, Pryjma J, Tarnok Z, Ernst M, Flad HD. Inhibitory and stimulatory effects of Pseudomonas aeruginosa pyocyanine on human T and B lymphocytes and human monocytes. Infect Immun. 1990;58:808–15.PubMedGoogle Scholar
  82. 82.
    Miller KM, Dearborn DG, Sorensen RU. In vitro effect of synthetic pyocyanine on neutrophil superoxide production. Infect Immun. 1987;55:559–63.PubMedGoogle Scholar
  83. 83.
    Ras GJ, Anderson R, Taylor GW, Savage JE, Van Niekerk E, Wilson R, et al. Proinflammatory interactions of pyocyanin and 1-hydroxyphenazine with human neutrophils in vitro. J Infect Dis. 1990;162:178–85.PubMedGoogle Scholar
  84. 84.
    Muller M, Sorrell TC. Modulation of neutrophil superoxide response and intracellular diacylglyceride levels by the bacterial pigment pyocyanin. Infect Immun. 1997;65:2483–7.PubMedGoogle Scholar
  85. 85.
    Muller M, Sorrell TC. Production of leukotriene B4 and 5-hydroxyeicosatetraenoic acid by human neutrophils is inhibited by Pseudomonas aeruginosa phenazine derivatives. Infect Immun. 1991;59:3316–8.PubMedGoogle Scholar
  86. 86.
    Muller M, Sorrell TC. Leukotriene B4 omega-oxidation by human polymorphonuclear leukocytes is inhibited by pyocyanin, a phenazine derivative produced by Pseudomonas aeruginosa. Infect Immun. 1992;60:2536–40.PubMedGoogle Scholar
  87. 87.
    Nutman J, Berger M, Chase PA, Dearborn DG, Miller KM, Waller RL, et al. Studies on the mechanism of T cell inhibition by the Pseudomonas aeruginosa phenazine pigment pyocyanine. J Immunol. 1987;138:3481–7.PubMedGoogle Scholar
  88. 88.
    Nutman J, Chase PA, Dearborn DG, Berger M, Sorensen RU. Suppression of lymphocyte proliferation by Pseudomonas aeruginosa phenazine pigments. Isr J Med Sci. 1988;24:228–32.PubMedGoogle Scholar
  89. 89.
    Cheluvappa R, Jamieson HA, Hilmer SN, Muller M, Le Couteur DG. The effect of Pseudomonas aeruginosa virulence factor, pyocyanin, on the liver sinusoidal endothelial cell. J Gastroenterol Hepatol. 2007;22:1350–1.PubMedCrossRefGoogle Scholar
  90. 90.
    Britigan BE, Roeder TL, Rasmussen GT, Shasby DM, McCormick ML, Cox CD. Interaction of the Pseudomonas aeruginosa secretory products pyocyanin and pyochelin generates hydroxyl radical and causes synergistic damage to endothelial cells. Implications for Pseudomonas-associated tissue injury. J Clin Invest. 1992;90:2187–96.PubMedCrossRefGoogle Scholar
  91. 91.
    Kamath JM, Britigan BE, Cox CD, Shasby DM: Pyocyanin from Pseudomonas aeruginosa inhibits prostacyclin release from endothelial cells. Infect Immun. 1995;63:4921–3.PubMedGoogle Scholar
  92. 92.
    Warren JB, Loi R, Rendell NB, Taylor GW. Nitric oxide is inactivated by the bacterial pigment pyocyanin. Biochem J. 1990;266:921–3.PubMedGoogle Scholar
  93. 93.
    Muller M. Pyocyanin induces oxidative stress in human endothelial cells and modulates the glutathione redox cycle. Free Radic Biol Med. 2002;33:1527–33.PubMedCrossRefGoogle Scholar
  94. 94.
    Muller M, Sztelma K, Sorrell TC. Inhibition of platelet eicosanoid metabolism by the bacterial phenazine derivative pyocyanin. Ann N Y Acad Sci. 1994;744:320–2.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  1. 1.Laboratory of Host DefensesNational Institutes of Health, National Institute of Allergy and Infectious DiseasesRockvilleUSA

Personalised recommendations