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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Sep 3;93(18):9553–9558. doi: 10.1073/pnas.93.18.9553

Cytokine-treated human neutrophils contain inducible nitric oxide synthase that produces nitration of ingested bacteria.

T J Evans 1, L D Buttery 1, A Carpenter 1, D R Springall 1, J M Polak 1, J Cohen 1
PMCID: PMC38466  PMID: 8790368

Abstract

Although the production of NO within rodent phagocytes is well-characterized, its production and function within human phagocytes are less clear. We show here that neutrophils within human buffy coat preparations stimulated with a mixture of interleukin 1, tumor necrosis factor alpha, and interferon gamma contain inducible NO synthase mRNA and protein, one of the enzymes responsible for NO production. The protein colocalizes with myeloperoxidase within neutrophil primary granules. Using an inhibitor of NO synthase, L-N-monomethyl arginine, we show that activity of this enzyme is required for the formation of nitrotyrosine around phagocytosed bacteria, most likely through the intermediate production of peroxynitrite, a reaction product of NO and superoxide anions.

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Selected References

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  1. Beckman J. S., Beckman T. W., Chen J., Marshall P. A., Freeman B. A. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1620–1624. doi: 10.1073/pnas.87.4.1620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beckman J. S., Ischiropoulos H., Zhu L., van der Woerd M., Smith C., Chen J., Harrison J., Martin J. C., Tsai M. Kinetics of superoxide dismutase- and iron-catalyzed nitration of phenolics by peroxynitrite. Arch Biochem Biophys. 1992 Nov 1;298(2):438–445. doi: 10.1016/0003-9861(92)90432-v. [DOI] [PubMed] [Google Scholar]
  3. Beckman J. S., Siedow J. N. Bactericidal agents generated by the peroxidase-catalyzed oxidation of para-hydroquinones. J Biol Chem. 1985 Nov 25;260(27):14604–14609. [PubMed] [Google Scholar]
  4. Beckmann J. S., Ye Y. Z., Anderson P. G., Chen J., Accavitti M. A., Tarpey M. M., White C. R. Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry. Biol Chem Hoppe Seyler. 1994 Feb;375(2):81–88. doi: 10.1515/bchm3.1994.375.2.81. [DOI] [PubMed] [Google Scholar]
  5. Bennett T. A., Schammel C. M., Lynam E. B., Guyer D. A., Mellors A., Edwards B., Rogelj S., Sklar L. A. Evidence for a third component in neutrophil aggregation: potential roles of O-linked glycoproteins as L-selectin counter-structures. J Leukoc Biol. 1995 Nov;58(5):510–518. doi: 10.1002/jlb.58.5.510. [DOI] [PubMed] [Google Scholar]
  6. Carreras M. C., Catz S. D., Pargament G. A., Del Bosco C. G., Poderoso J. J. Decreased production of nitric oxide by human neutrophils during septic multiple organ dysfunction syndrome. Comparison with endotoxin and cytokine effects on normal cells. Inflammation. 1994 Apr;18(2):151–161. doi: 10.1007/BF01534556. [DOI] [PubMed] [Google Scholar]
  7. Carreras M. C., Pargament G. A., Catz S. D., Poderoso J. J., Boveris A. Kinetics of nitric oxide and hydrogen peroxide production and formation of peroxynitrite during the respiratory burst of human neutrophils. FEBS Lett. 1994 Mar 14;341(1):65–68. doi: 10.1016/0014-5793(94)80241-6. [DOI] [PubMed] [Google Scholar]
  8. Cohen M. S. Molecular events in the activation of human neutrophils for microbial killing. Clin Infect Dis. 1994 Feb;18 (Suppl 2):S170–S179. doi: 10.1093/clinids/18.supplement_2.s170. [DOI] [PubMed] [Google Scholar]
  9. Floris R., Piersma S. R., Yang G., Jones P., Wever R. Interaction of myeloperoxidase with peroxynitrite. A comparison with lactoperoxidase, horseradish peroxidase and catalase. Eur J Biochem. 1993 Aug 1;215(3):767–775. doi: 10.1111/j.1432-1033.1993.tb18091.x. [DOI] [PubMed] [Google Scholar]
  10. Fujishima S., Aikawa N. Neutrophil-mediated tissue injury and its modulation. Intensive Care Med. 1995 Mar;21(3):277–285. doi: 10.1007/BF01701489. [DOI] [PubMed] [Google Scholar]
  11. Garthwaite J., Charles S. L., Chess-Williams R. Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature. 1988 Nov 24;336(6197):385–388. doi: 10.1038/336385a0. [DOI] [PubMed] [Google Scholar]
  12. Goode H. F., Webster N. R., Howdle P. D., Walker B. E. Nitric oxide production by human peripheral blood polymorphonuclear leucocytes. Clin Sci (Lond) 1994 Apr;86(4):411–415. doi: 10.1042/cs0860411. [DOI] [PubMed] [Google Scholar]
  13. Haddad I. Y., Crow J. P., Hu P., Ye Y., Beckman J., Matalon S. Concurrent generation of nitric oxide and superoxide damages surfactant protein A. Am J Physiol. 1994 Sep;267(3 Pt 1):L242–L249. doi: 10.1152/ajplung.1994.267.3.L242. [DOI] [PubMed] [Google Scholar]
  14. Haddad I. Y., Pataki G., Hu P., Galliani C., Beckman J. S., Matalon S. Quantitation of nitrotyrosine levels in lung sections of patients and animals with acute lung injury. J Clin Invest. 1994 Dec;94(6):2407–2413. doi: 10.1172/JCI117607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hibbs J. B., Jr, Vavrin Z., Taintor R. R. L-arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells. J Immunol. 1987 Jan 15;138(2):550–565. [PubMed] [Google Scholar]
  16. Ischiropoulos H., Zhu L., Chen J., Tsai M., Martin J. C., Smith C. D., Beckman J. S. Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch Biochem Biophys. 1992 Nov 1;298(2):431–437. doi: 10.1016/0003-9861(92)90431-u. [DOI] [PubMed] [Google Scholar]
  17. Kilbourn R. G., Griffith O. W. Overproduction of nitric oxide in cytokine-mediated and septic shock. J Natl Cancer Inst. 1992 Jun 3;84(11):827–831. doi: 10.1093/jnci/84.11.827. [DOI] [PubMed] [Google Scholar]
  18. Kolls J., Xie J., LeBlanc R., Malinski T., Nelson S., Summer W., Greenberg S. S. Rapid induction of messenger RNA for nitric oxide synthase II in rat neutrophils in vivo by endotoxin and its suppression by prednisolone. Proc Soc Exp Biol Med. 1994 Mar;205(3):220–229. doi: 10.3181/00379727-205-43700. [DOI] [PubMed] [Google Scholar]
  19. Kooy N. W., Royall J. A., Ye Y. Z., Kelly D. R., Beckman J. S. Evidence for in vivo peroxynitrite production in human acute lung injury. Am J Respir Crit Care Med. 1995 Apr;151(4):1250–1254. doi: 10.1164/ajrccm/151.4.1250. [DOI] [PubMed] [Google Scholar]
  20. Lorsbach R. B., Murphy W. J., Lowenstein C. J., Snyder S. H., Russell S. W. Expression of the nitric oxide synthase gene in mouse macrophages activated for tumor cell killing. Molecular basis for the synergy between interferon-gamma and lipopolysaccharide. J Biol Chem. 1993 Jan 25;268(3):1908–1913. [PubMed] [Google Scholar]
  21. Malawista S. E., Montgomery R. R., van Blaricom G. Evidence for reactive nitrogen intermediates in killing of staphylococci by human neutrophil cytoplasts. A new microbicidal pathway for polymorphonuclear leukocytes. J Clin Invest. 1992 Aug;90(2):631–636. doi: 10.1172/JCI115903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McCall T. B., Boughton-Smith N. K., Palmer R. M., Whittle B. J., Moncada S. Synthesis of nitric oxide from L-arginine by neutrophils. Release and interaction with superoxide anion. Biochem J. 1989 Jul 1;261(1):293–296. doi: 10.1042/bj2610293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. McCall T. B., Palmer R. M., Moncada S. Induction of nitric oxide synthase in rat peritoneal neutrophils and its inhibition by dexamethasone. Eur J Immunol. 1991 Oct;21(10):2523–2527. doi: 10.1002/eji.1830211032. [DOI] [PubMed] [Google Scholar]
  24. Mirza U. A., Chait B. T., Lander H. M. Monitoring reactions of nitric oxide with peptides and proteins by electrospray ionization-mass spectrometry. J Biol Chem. 1995 Jul 21;270(29):17185–17188. doi: 10.1074/jbc.270.29.17185. [DOI] [PubMed] [Google Scholar]
  25. Nathan C. F., Hibbs J. B., Jr Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr Opin Immunol. 1991 Feb;3(1):65–70. doi: 10.1016/0952-7915(91)90079-g. [DOI] [PubMed] [Google Scholar]
  26. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992 Sep;6(12):3051–3064. [PubMed] [Google Scholar]
  27. Oury T. D., Tatro L., Ghio A. J., Piantadosi C. A. Nitration of tyrosine by hydrogen peroxide and nitrite. Free Radic Res. 1995 Dec;23(6):537–547. doi: 10.3109/10715769509065275. [DOI] [PubMed] [Google Scholar]
  28. Padgett E. L., Pruett S. B. Rat, mouse and human neutrophils stimulated by a variety of activating agents produce much less nitrite than rodent macrophages. Immunology. 1995 Jan;84(1):135–141. [PMC free article] [PubMed] [Google Scholar]
  29. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  30. Radi R., Beckman J. S., Bush K. M., Freeman B. A. Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys. 1991 Aug 1;288(2):481–487. doi: 10.1016/0003-9861(91)90224-7. [DOI] [PubMed] [Google Scholar]
  31. Salvemini D., de Nucci G., Gryglewski R. J., Vane J. R. Human neutrophils and mononuclear cells inhibit platelet aggregation by releasing a nitric oxide-like factor. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6328–6332. doi: 10.1073/pnas.86.16.6328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sampson J. B., Rosen H., Beckman J. S. Peroxynitrite-dependent tyrosine nitration catalyzed by superoxide dismutase, myeloperoxidase, and horseradish peroxidase. Methods Enzymol. 1996;269:210–218. doi: 10.1016/s0076-6879(96)69023-5. [DOI] [PubMed] [Google Scholar]
  33. Schmidt H. H., Seifert R., Böhme E. Formation and release of nitric oxide from human neutrophils and HL-60 cells induced by a chemotactic peptide, platelet activating factor and leukotriene B4. FEBS Lett. 1989 Feb 27;244(2):357–360. doi: 10.1016/0014-5793(89)80562-9. [DOI] [PubMed] [Google Scholar]
  34. Sherman P. A., Laubach V. E., Reep B. R., Wood E. R. Purification and cDNA sequence of an inducible nitric oxide synthase from a human tumor cell line. Biochemistry. 1993 Nov 2;32(43):11600–11605. doi: 10.1021/bi00094a017. [DOI] [PubMed] [Google Scholar]
  35. Xie Q. W., Cho H. J., Calaycay J., Mumford R. A., Swiderek K. M., Lee T. D., Ding A., Troso T., Nathan C. Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science. 1992 Apr 10;256(5054):225–228. doi: 10.1126/science.1373522. [DOI] [PubMed] [Google Scholar]
  36. Yan L., Vandivier R. W., Suffredini A. F., Danner R. L. Human polymorphonuclear leukocytes lack detectable nitric oxide synthase activity. J Immunol. 1994 Aug 15;153(4):1825–1834. [PubMed] [Google Scholar]
  37. Zhu L., Gunn C., Beckman J. S. Bactericidal activity of peroxynitrite. Arch Biochem Biophys. 1992 Nov 1;298(2):452–457. doi: 10.1016/0003-9861(92)90434-x. [DOI] [PubMed] [Google Scholar]

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