Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity

Current Opinion in Immunology

Volumn 12, Issue 1, 2000, Pages 64-76

  Bogdan, Christian ^a   Röllinghoff, Martin ^a   Diefenbach, Andreas ^b  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKINE; GAMMA INTERFERON; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; REACTIVE OXYGEN METABOLITE; TUMOR NECROSIS FACTOR ALPHA;

APOPTOSIS; IMMUNE RESPONSE; IMMUNITY; INFECTION; LYMPHOCYTE ACTIVATION; REVIEW; SIGNAL TRANSDUCTION;

EID: 17544404224     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0952-7915(99)00052-7     Document Type: Review

References (139)

1. Klebanoff S.J. Oxygen metabolites from phagocytes. Gallin J.I., Snyderman R. Inflammation: Basic Principles and Clinical Correlates. 1999;721-768 Lippincott Williams & Wilkins, Philadelphia.
2. Lenaz G. Oxidants in mitochondria: from physiology to diseases. Biochim Biophys Acta. 1271:1995;67-74.
3. Xia Y., Roman L.J., Masters B.S.S., Zweier J.L. Inducible nitric oxide synthase generates superoxide from the reductase domain. J Biol Chem. 273:1998;22635-22639.
4. MacMicking J., Xie Q-w., Nathan C. Nitric oxide and macrophage function. Annu Rev Immunol. 15:1997;323-350.
5. Bogdan C. The function of nitric oxide in the immune system. Mayer B. Handbook of Experimental Pharmacology: Nitric Oxide. 2000;443-493 Springer, Heidelberg. The review covers about 400 original papers on the regulation and function of NO in the immune system.
6. Michel T., Feron O. Nitric oxide synthases: which, where, how, and why? J Clin Invest. 100:1997;2146-2152.
7. Tatoyan A., Giulivi C. Purification and characterization of a nitric oxide synthase from rat liver mitochondria. J Biol Chem. 273:1998;11044-11048.
8. Schmidt H.H.H.W., Hofmann H., Schindler U., Shutenko Z., Cunningham D.D., Feelisch M. No ·NO from NO synthase. Proc Natl Acad Sci USA. 93:1996;14492-14497.
9. Gow A.J., Stamler J.S. Reactions between nitric oxide and haemoglobin under physiological conditions. Nature. 391:1998;169-173.
10. + Th1 cells induce NOS2 whereas Th2 cells upregulate arginase without induction of NOS2. This dichotomy might contribute to the differential state of macrophage activation in Th1 responses compared with Th2 responses.
11. Ding A.H., Nathan C.F., Stuehr D.J. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol. 141:1988;2407-2412.
12. Sharara A.I., Perkins D.J., Misukonis M.A., Chan S.U., Dominitz J.A., Weinberg B.J. Interferon-α activation of human blood mononuclear cells in vitro and in vivo for nitric oxide synthase (NOS) type 2 mRNA and protein expression: possible relationship of induced NOS2 to the anti-hepatitis C effects of IFN-α in vivo. J Exp Med. 186:1997;1495-1502.
13. Diefenbach A., Schindler H., Donhauser N., Lorenz E., Laskay T., MacMicking J., Röllinghoff M., Gresser I., Bogdan C. Type 1 interferon (IFN-α/β) and type 2 nitric oxide synthase regulate the innate immune response to a protozoan parasite. Immunity. 8:1998;77-87. IFN-α/β is identified as the principal inducer of focally expressed NOS2 at day 1 of infection with L. major. In addition to antimicrobial activities, NOS2-derived NO is shown to be indispensable for the innate immune response (NK cell cytotoxic activity and IFN-γ production) and to downregulate early TGF-β production.
14. Lopez-Collazo E., Hortelano S., Rojas A., Bosca L. Triggering of peritoneal macrophages with IFN-α/β attenuates the expression of inducible nitric oxide through a decrease in NF-κB activation. J Immunol. 160:1998;2889-2895. This is the first study to provide a molecular mechanism for the antagonistic effect of IFN-α/β on the expression of NOS2 and also shows that IFN-γ activates NF-κB in macrophages.
15. Hirji N., Lin T-J., Bissonnette E., Belosevic M., Befus A.D. Mechanisms of macrophage stimulation through CD8: CD8α and CD8β induce nitric oxide production and subsequent killing of the parasite Leishmainia major. J Immunol. 160:1998;6004-6011.
16. 2B adenosine receptor expression in macrophages: a mechanism of macrophage deactivation. J Immunol. 162:1999;3607-3614. Macrophage deactivation is critical for limiting an inflammatory response. This study shows that the activating cytokine itself (IFN-γ) triggers a feedback mechanism that downregulates macrophage NO production.
17. Gao J.J., Filla M.B., Fultz M.J., Vogel S.N., Russell S.W., Murphy W.J. Autocrine/paracrine IFN-α/β mediates the lipopolysaccharide-induced activation of transcription factor Stat1α in mouse macrophages: pivotal role of Stat1α in induction of the inducible nitric oxide synthase gene. J Immunol. 161:1998;4803-4810.
18. Brightbill H.D., Libraty D.H., Krutzik S.R., Yang R-B., Belisle J.T., Bleharski J.R., Maitland M., Norgard M.V., Plevy S.E., Smale S.T.et al. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science. 285:1999;732-734. The first study to demonstrate that microbial lipoproteins (other than LPS) require Toll-receptor-2 signalling for the production of IL-12 and the induction of NOS2 in macrophages.
19. Braun J.S., Novak R., Gao G., Murray P.J., Shenep J.L. Pneumolysin, a protein toxin of Streptococcus pneumoniae, induces nitric oxide production from macrophages. Infect Immun. 67:1999;3750-3756.
20. Flak T.A., Goldman W.E. Signaling and cellular specificity of airway nitric oxide production in pertussis. Cell Microbiol. 1:1999;51-60. B. pertussis tracheal cytotoxin together with LPS induces NOS2 exclusively in nonciliated (secretory) epithelial cells. The released NO then damages the nearby ciliated epithelial cells, which is thought to be a critical process in the pathogenesis of pertussis.
21. Nandan D., Lo R., Reiner N.E. Activation of phosphotyrosine phosphatase activity attenuates mitogen-activated protein kinase signaling and inhibits c-fos and nitric oxide synthase expression in macrophages infected with Leishmania donovani. Infect Immun. 67:1999;4055-4063. The authors have previously shown that L. donovani interferes with the tyrosine phosphorylation of Jak1/Jak2/Stat1 signalling pathway. The present work shows that other signalling pathways are also affected.
22. Chinen T., Qureshi M.H., Koguchi Y., Kawakami K. Candida albicans suppresses nitric oxide (NO) production by interferon (IFN)-γ and lipopolysacchride (LPS)-stimulated murine peritoneal macrophages. Clin Exp Immunol. 115:1999;491-497.
23. Chen W., Syldath U., Bellmann K., Burkart V., Kolb H. Human 60 kDa heat-shock protein: a danger signal to the innate immune system. J Immunol. 162:1999;3212-3219. This study suggests that a noncytokine host protein released during (microbial) tissue damage might serve to upregulate macrophage activity (i.e. production of NO, TNF-α, IL-12 and IL-15).
24. Weiss G., Bogdan C., Hentze M.W. Pathways for the regulation of macrophage iron metabolism by the anti-inflammatory cytokines IL-4 and IL-13. J Immunol. 158:1997;420-425.
25. Melillo G., Taylor L.S., Brooks A., Musso T., Cox G.W., Varesio L. Functional requirement of the hypoxia-responsive element in the activation of the inducible nitric oxide synthase promotor by the iron chelator desferrioxamine. J Biol Chem. 272:1997;12236-12243.
26. Bellocq A., Suberville S., Philippe C., Bertrand F., Perez J., Fouqueray B., Cherqui G., Baud L. Low environmental pH is responsible for the induction of nitric oxide synthase in macrophages. J Biol Chem. 273:1998;5086-5092.
27. Doherty T.M., Sher A., Vogel S.N. Paclitaxel (taxol)-induced killing of Leishmania major in murine macrophages. Infect Immun. 66:1998;4553-4556.
28. D'Agostino P., La Rosa M., Barbera C., Arcoleo F., Di Bella G., Milano S., Cillari E. Doxycycline reduces mortality to lethal endotoxemia by reducing nitric oxide synthesis via an interleukin 10-independent mechanism. J Infect Dis. 177:1998;489-492.
29. Sennequier N., Wolan D., Stuehr D.J. Antifungal imidazoles block assembly of inducible NO synthase into an active dimer. J Biol Chem. 274:1999;930-938.
30. phox-independent mechanism of killing of L. monocytogenes and S. typhimurium.
31. Diefenbach A., Schindler H., Röllinghoff M., Yokoyama W., Bogdan C. Requirement for type 2 NO-synthase for IL-12 responsiveness in innate immunity. Science. 284:1999;951-955. NOS2-derived NO is a prerequisite for IL-12- or IFN-α/β-induced activation of NK cells because it functions as a cosignal for the activation of Tyk2 kinase. NO-dependency of IL-12 responsiveness is also documented in vivo during the early phase of L. major infection.
32. Karupiah G., Chen J-H., Mahalingam S., Nathan C.F., MacMicking J.D. Rapid interferon γ-dependent clearance of influenza A virus and protection from consolidating pneumonitis in nitric oxide 2-deficient mice. J Exp Med. 188:1998;1541-1546.
33. Wei X-Q., Charles I.G., Smith A., Ure J., Feng G-J., Huang F-P., Xu D., Müller W., Moncada S., Liew F.Y. Altered immune responses in mice lacking inducible nitric oxide synthase. Nature. 375:1995;408-411.
34. Niedbala W., Wei X-Q., Piedrafita D., Xu D., Liew F.Y. Effects of nitric oxide on the induction and differentiation of Th1 cells. Eur J Immunol. 29:1999;2498-2505. First study showing a dose-dependent effect of an NO donor on the development of IFN-γ-producing Th cells in vitro.
35. Huang F-P., Xu D., Esfandiari E-O., Sands W., Wei X-Q., Liew F.Y. Mice defective in Fas are highly susceptible to Leishmania major infection despite elevated IL-12 synthesis, strong Th1 responses, and enhanced nitric oxide production. J Immunol. 160:1998;4143-4147.
36. Fang F.C. Mechanisms of nitric oxide-related antimicrobial activity. J Clin Invest. 99:1997;2818-2825.
37. Andonegui G., Trevani A.S., Gamberale R., Carreras M.C., Poderoso J.J., Giordano M., Geffner J.R. Effect of nitric oxide donors on oxygen-dependent cytotoxic responses by neutrophils. J Immunol. 162:1999;2922-2930.
38. Saura M., Zaragoza C., McMillan A., Quick R.A., Hohenadl C., Lowenstein J.M., Lowenstein C.J. An antiviral mechanism of nitric oxide: inhibition of a viral protease. Immunity. 10:1999;21-28. This is the first example of an infectious agent (Coxsackie virus), for which the molecule inactivated by NO during the intracellular life cycle has been defined.
39. Mnaimneh S., Geffard M., Veyret B., Vincendeau P. Albumin nitrosylated by activated macrophages possesses antiparasitic effects neutralized by anti-NO-acetylated-cysteine antibodies. J Immunol. 158:1997;308-314.
40. Hickman-Davis J., Gibbs-Erwin J., Lindsey J.R., Matalon S. Surfactant protein A mediates mycoplasmacidal activity of alveolar macrophages by production of peroxynitrite. Proc Natl Acad Sci USA. 96:1999;4953-4958.
41. Nagata K., Yu H., Nishikawa M., Kashiba M., Nakamura A., Sato E.F., Tamura T., Inoue M. Helicobacter pylori generates superoxide radicals and modulates nitric oxide metabolism. J Biol Chem. 273:1998;14071-14073.
42. Fujii H., Ichimori K., Hoshiai K., Nakazawa H. Nitric oxide inactivates NADPH oxidase in pig neutrophils by inhibiting its assembling process. J Biol Chem. 272:1997;32773-32778.
43. Aratani Y., Koyoma H., Nyui S-I., Suzuki K., Kura F., Maeda N. Severe impairment in early host defense against Candida albicans in mice deficient in myeloperoxidase. Infect Immun. 67:1999;1828-1836.
44. Borelli V., Banfi E., Perrotta M.G., Zabucchi G. Myeloperoxidase exerts microbicidal activity against Mycobacterium tuberculosis. Infect Immun. 67:1999;4149-4152.
45. Nguyen C., Katner H.P. Myeloperoxidase deficiency manifesting as pustular candidal dermatitis. Clin Infect Dis. 24:1997;258-260.
46. Eiserich J.P., Hristova M., Cross C.E., Jones A.D., Freeman B.A., Halliwell B., van der Vliet A. Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. Nature. 391:1998;393-397. This study defines a new function of MPO within granulocytes and provides evidence for an unexpected convergence of the ROI and RNI pathways.
47. Eiserich J.P., Schultz J., Bamberg T.V., Nauseef W.M., Freeman B.A. Nitration reactions catalyzed by interactions of the peroxidase and nitric oxide synthase pathways: eosinophil peroxidase compensates for myeloperoxidase deficiency. Acta Physiol Scand. 167(suppl 645):1999;19. [abstract].
48. Evans T.J., Buttery L.D.K., Carpenter A., Springall D.R., Polak J.M., Cohen J. Cytokine-treated human neutrophils contain inducible nitric oxide synthase that produces nitration of ingested bacteria. Proc Natl Acad Sci USA. 93:1996;9553-9558.
49. Manca C., Paul S., Barry C.E., Freedman V.H., Kaplan G. Mycobacterium tuberculosis catalase and peroxidase activities and resistance to oxidative killing in human monocytes in vitro. Infect Immun. 67:1999;74-79.
50. De Groote M.A., Ochsner U.A., Shiloh M., McCord J.M., Dinauer M.C., Libby S.J., Vazquez-Torres A., Xu Y., Fang F.C. Periplasmic superoxide dismutase protects Salmonella from products of phagocyte oxidase and nitric oxide synthase. Proc Natl Acad Sci USA. 94:1997;13997-14001.
51. Hausladen A., Privalle C.T., Keng T., DeAngelo J., Stamler J.S. Nitrosative stress: activation of the transcription factor oxyR. Cell. 86:1996;719-729.
52. Chen L., Xie Q-W., Nathan C. Alkyl hydroperoxide reductase subunit C (AhpC) protects bacterial and human cells against reactive nitrogen intermediates. Mol Cell. 1:1998;795-805. This study as well as previous work by the same group have pioneered the field of microbial resistance to NO by the identification of (novel) genes that are widely spread (ahpC) and express anti-RNI functions.
53. Crawford M.J., Goldberg D.E. Regulation of the Salmonella typhimurium flavohemoglobin gene. A new pathway for bacterial gene expression in response to nitric oxide. J Biol Chem. 273:1998;34028-34032.
54. Gardner P.R., Gardner A.M., Martin L.A., Salzman A.L. Nitric oxide dioxygenase: an enzymatic function for flavohemoglobin. Proc Natl Acad Sci USA. 95:1998;10378-10383.
55. Hausladen A., Gow A.J., Stamler J.S. Nitrosative stress: metabolic pathway involving the flavohemoglobin. Proc Natl Acad Sci USA. 95:1998;14100-14105.
56. de Groote M.A., Testerman T., Xu Y., Stauffer G., Fang F.C. Homocysteine antagonism of nitric oxide-related cytostasis in Salmonella typhimurium. Science. 272:1996;414-417.
57. Ruan J., John G.S., Ehrt S., Riley L., Nathan C. noxR3, a novel gene from Mycobacterium tuberculosis, protects Salmonella typhimurium from nitrosative and oxidative stress. Infect Immun. 67:1999;3276-3283.
58. Miyamoto Y., Akaike T., Kuwahara H., Kubota T., Yoshimatsu S., Sawa T., Okamoto S., Maeda H. Urease function as a defense system of Helicobacter pylori against peroxynitrite through production of carbon monoxide. Acta Physiol Scand. 167(suppl 645):1999;17. [abstract].
59. Mehlotra R.K. Antioxidant defense mechanisms in parasitic protozoa. Crit Rev Microbiol. 22:1996;295-314.
60. Schnitzler N., Peltroche-Llacsahuanga H., Bestier N., Zündorf J., Lütticken R., Haase G. Effect of melanin and carotenoids of Exophiala (Wangiella) dermatitidis on phagocytosis, oxidative burst, and killing by human neutrophils. Infect Immun. 67:1999;94-101.
61. Rothe H., Hartmann B., Geerlings P., Kolb H. Interleukin-12 gene expression of macrophages is regulated by nitric oxide. Biochem Biophys Res Commun. 224:1996;159-163.
62. Huang F-P., Niedbala W., Wei X-Q., Xu D., Feng G-J., Robinson J.H., Lam C., Liew F.Y. Nitric oxide regulates Th1 cell development through the inhibition of IL-12 synthesis by macrophages. Eur J Immunol. 28:1998;4062-4070.
63. Mullins D.W., Burger C.J., Elgert K.D. Paclitaxel enhances macrophage IL-12 production in tumor-bearing hosts through nitric oxide. J Immunol. 162:1999;6811-6818.
64. Salvucci O., Kolb J.P., Dugas B., Dugas N., Chouaib S. The induction of nitric oxide by interleukin-12 and tumor necrosis factor-alpha in human natural killer cells: relationship with the regulation of lytic activity. Blood. 92:1998;2093-2102.
65. ••]).
66. Taylor-Robinson A.W., Liew F.Y., Severn A., Xu D., McScorley S.J., Garside P., Padron J., Phillips R.S. Regulation of the immune response by nitric oxide differentially produced by T helper type 1 and T helper type 2 cells. Eur J Immunol. 24:1994;980-984.
67. Thüring H., Stenger S., Gmehling D., Röllinghoff M., Bogdan C. Lack of inducible nitric oxide synthase activity in T cell-clones and T lymphocytes from naive and Leishmania major-infected mice. Eur J Immunol. 25:1995;3229-3234.
68. Bauer H., Jung T., Tsikas D., Stichtenoth D.O., Fröhlich J.C., Neumann C. Nitric oxide inhibits the secretion of T-helper 1- and T-helper 2-associated cytokines in activated human T cells. Immunology. 90:1997;205-211.
69. Mannick J.B., Hausladen A., Liu L., Hess D.T., Zeng M., Miao Q.X., Kane L.S., Gow A.J., Stamler J.S. Fas-induced caspase denitrosylation. Science. 284:1999;651-654. S-nitrosylation is not only shown to occur under physiological conditions within mammalian T and B cells but is also demonstrated to be functional and to be regulated by an immunological stimulus.
70. Marcinkiewicz J., Grabowska A., Chain B.M. Is there a role for nitric oxide in regulation of T cell secretion of IL-2? J Immunol. 156:1996;4617-4621.
71. Chang R-H., Lin Feng M-H., Liu W-H., Lai M-Z. Nitric oxide increased interleukin-4 expression in T lymphocytes. Immunology. 90:1997;364-369.
72. van der Veen R.C., Dietlin T.A., Pen L., Gray J.D. Nitric oxide inhibits the proliferation of T-helper 1 and 2 lymphocytes without reduction in cytokine secretion. Cell Immunol. 193:1999;194-201.
73. -/- mouse model of chronic granulomatous disease has normal granuloma formation and cytokine responses to Mycobacterium avium and Schistosoma mansoni eggs. Infect Immun. 67:1999;1659-1665.
74. Morgenstern D.E., Gifford M.A.C., Li L.L., Doerschuk C.M., Dinauer M.C. Absence of respiratory burst in X-linked chronic granulomatous disease mice leads to abnormalities in both host defense and inflammatory response to Aspergillus fumigatus. J Exp Med. 185:1997;207-218.
75. Glockzin S., von Knethen A., Scheffner M., Brüne B. Activation of the cell death program by nitric oxide involves inhibition of the proteasome. J Biol Chem. 274:1999;19581-19586. This paper shows that NO regulates a basic pathway of protein degradation in mammalian cells and links this to the proapoptotic function of NO.
76. Brito C., Naviliat M., Tiscornia A.C., Vuillier F., Gualco G., Dighiero G., Radi R., Cayota A.M. Peroxynitrite inhibits T lymphocyte activation and proliferation by promoting impairment of tyrosine phosphorylation and peroxinitrite-driven apoptotic death. J Immunol. 162:1999;3356-3366.
77. Stassi G., de Maria R., Trucco G., Rudert W., Testi R., Galluzzo A., Giordano C., Trucco M. Nitric oxide primes pancreatic β cells for Fas-mediated destruction in insulin-dependent diabetes mellitus. J Exp Med. 186:1997;1193-1200.
78. Williams M.S., Noguchi S., Henkart P.S., Osawa Y. Nitric oxide synthase plays a signalling role in TCR-triggered apoptotic death. J Immunol. 161:1998;6526-6531. First study that shows that NO derived from constitutive NOS (NOS1) is functional within T lymphocytes.
79. Martins G.A., Vieira L.Q., Cunha F.Q., Silva J.S. Gamma interferon modulates CD95 (Fas) and CD95 ligand (FasL) expression and nitric oxide-induced apoptosis during the acute phase of Trypanosoma cruzi infection: a possible role in immune response control. Infect Immun. 67:1999;3864-3871.
80. Tai X-G., Toyo-Oka K., Yamamoto N., Yashiro Y., Mu J., Hamaoka T., Fujiwara H. Expression of an inducible type of nitric oxide (NO) synthase in the thymus and involvement of NO in deletion of TCR-stimulated double-positive thymocytes. J Immunol. 158:1997;4696-4703.
81. Tarrant T.K., Silver P.B., Wahlsten J.L., Rizzo L.V., Chan C-C., Wiggert B., Caspi R.R. Interleukin-12 protects from a Th1-mediated autoimmune disease, experimental autoimmune uveitis, through a mechanism involving IFN-γ, nitric oxide and apoptosis. J Exp Med. 189:1999;219-230. This paper challenges the view that IL-12 always favours the development of Th1 cells. IL-12 is shown to counteract Th1-mediated processes via induction of IFN-γ, NOS2 and apoptosis.
82. von Knethen A., Callsen D., Brüne B. NF-κB and AP-1 activation by nitric oxide attenuated apoptotic cell death in RAW 264.7 macrophages. Mol Biol Cell. 10:1999;361-372.
83. Hebestreit H., Dibbert B., Balatti I., Braun D., Schapowal A., Blaser K., Simon H-U. Disruption of Fas receptor signaling by nitric oxide in eosinophils. J Exp Med. 187:1998;415-425.
84. Rössig L., Fichtlscherer B., Breitschopf K., Haendeler J., Zeiher A.M., Mülsch A., Dimmeler S. Nitric oxide inhibits caspase-3 by S-nitrosation in vivo. J Biol Chem. 274:1999;6823-6826.
85. Li J., Bombeck C.A., Yang S., Kim Y-M., Billiar T.R. Nitric oxide suppresses apoptosis via interrupting caspase activation and mitochondrial dysfunction in cultured hepatocytes. J Biol Chem. 274:1999;17325-17333.
86. Rai R.M., Lee F.Y.J., Rosen A., Yang S.Q., Lin H.Z., Koteish A., Liew F.Y., Zaragoza C., Lowenstein C., Diehl A.M. Impaired liver regeneration in inducible nitric oxide synthase-deficient mice. Proc Natl Acad Sci USA. 95:1998;13829-13834.
87. Melino G., Bernassola F., Knight R.A., Corasaniti M.T., Nistico G., Finazzi-Agro A. S-nitrosylation regulates apoptosis. Nature. 388:1997;432-433.
88. Hansson M., Asea A., Ersson U., Hermodsson S., Hellstrand K. Induction of apoptosis in NK cells by monocyte-derived reactive oxygen metabolites. J Immunol. 156:1996;42-47.
89. Brüne B., Götz C., Messmer U.K., Sandau K., Hirvonen M.R., Lapetina E.G. Superoxide formation and macrophage resistance to nitric oxide-mediated apoptosis. J Biol Chem. 272:1997;7253-7258.
90. Fadeel B., Ahlin A., Henter J-J., Orrenius S., Hampton M.B. Involvement of caspases in neutrophil apoptosis: regulation by reactive oxygen species. Blood. 92:1998;4808-4818.
91. Hildeman D.A., Mitchell T., Teague T.K., Henson P., Day B.J., Kappler J., Marrack P.C. Reactive oxygen species regulate activation-induced T cell apoptosis. Immunity. 10:1999;735-744. Characterization of a Fas/TNF-independent, but ROI-dependent pathway of cell death in T lymphocytes.
92. Lander H.M. An essential role for free radicals and derived species in signal transduction. FASEB J. 11:1997;118-124.
93. Li N., Karin M. Is NF-kB the sensor of oxidative stress? FASEB J. 13:1999;1137-1143.
94. Carballo M., Conde M., Bekay R.E., Martin-Nieto J., Camacho M.J., Monteseirin J., Conde J., Bedoya F.J., Sobrino F. Oxidative stress triggers Stat3 tyrosine phosphorylation and nuclear translocation in human lymphocytes. J Biol Chem. 274:1999;17580-17586.
95. Abe J.-I., Berk B.C. Fyn and Jak2 mediate Ras activation by reactive oxygen species. J Biol Chem. 274:1999;21003-21010.
96. Lander H.M., Jacovina A.T., Davis R.J., Tauras J.M. Differential activation of mitogen-activated protein kinases by nitric oxide-related species. J Biol Chem. 271:1996;19705-19709.
97. -/- mice) that the upregulation of the transcription factors NF-κB and Stat3 in the lung and liver following hemorrhagic shock is NOS2-dependent.
98. Duhé R.J., Evans G.A., Erwin R.A., Kirken R.A., Cox G.W., Farrar W.L. Nitric oxide and thiol redox regulation of Janus kinase activity. Proc Natl Acad Sci USA. 95:1998;126-131.
99. Bingisser R.M., Tilbrook P.A., Holt P.G., Kees U.R. Macrophage-derived nitric oxide regulates T cell activation via reversible disruption of the Jak3/Stat5 signaling pathway. J Immunol. 160:1998;5729-5734.
100. •]).
101. Browning D.D., Windes N.D., Ye R.D. Activation of p38 mitogen-activated protein kinase by lipopolysaccharide in human neutrophils requires nitric oxide-dependent cGMP accumulation. J Biol Chem. 274:1999;537-542.
102. Kim Y-M., Talanian R.V., Li J., Billiar T.R. Nitric oxide prevents IL-1β and IFN-γ-inducing factor (IL-18) release from macrophages by inhibiting caspase-1 (IL-1β-converting enzyme). J Immunol. 161:1998;4122-4128. First study to identify a cytokine-specific mechanism by which NO affects cytokine production by macrophages.
103. •].
104. Lahdenpohja N., Savinainen K., Hurme M. Pre-exposure to oxidative stress decreases the nuclear factor-κB-dependent transcription in T lymphocytes. J Immunol. 160:1998;1354-1358.
105. Cruz M.T., Carmo A., Carvalho A.P., Lopes M.C. Calcium-dependent nitric oxide synthase activity in rat thymocytes. Biochem Biophys Res Commun. 248:1998;98-103.
106. 2+/calmodulin-dependent isoform in human B and T lymphocytes. Eur J Immunol. 26:1996;511-516.
107. Komatsu T., Bi Z., Reiss C.S. IFN-γ induced type 1 nitric oxide synthase activity inhibits viral replication in neurons. J Neuroimmunol. 68:1996;101-108.
108. Barna M., Komatsu T., Reiss C.S. Activation of type III nitric oxide synthase in astrocytes following a neurotropic viral infection. Virology. 15:1996;332-343.
109. Delledonne M., Xia Y., Dixon R.A., Lamb C. Nitric oxide functions as a signal in plant disease resistance. Nature. 394:1998;585-588.
110. •]).
111. •].
112. Zaragoza C., Ocampo C., Saura M., Leppo M., Wei X-Q., Quick R., Moncada S., Liew F.Y., Lowenstein C.J. The role of inducible nitric oxide synthase in the host response to Coxsackievirus myocarditis. Proc Natl Acad Sci USA. 95:1998;2469-2474.
113. Karupiah G., Chen J.H., Nathan C.F., Mahalingam S., MacMicking J.D. Identification of nitric oxide synthase 2 as an innate resistance locus against ectromelia virus infection. J Virol. 72:1998;7703-7706.
114. MacLean A., Wei X.Q., Huang F.P., Al-Alem U.A., Chan W.L., Liew F.Y. Mice lacking inducible nitric oxide synthase are more susceptible to herpes simplex virus infection despite enhanced Th1 cell responses. J Gen Virol. 79:1998;825-830.
115. Ramsey K.H., Miranpuri G.S., Poulson C.E., Marthakis N.B., Braune L.M., Byrne G.I. Inducible nitric oxide synthase does not affect resolution of murine chlamydial genital tract infections or eradication of chlamydiae in primary murine cell culture. Infect Immun. 66:1998;835-838.
116. Perry L.L., Feilzer K., Caldwell H.D. Neither interleukin-6 nor inducible nitric oxide synthase is required for clearance of Chlamydia trachomatis from the murine genital tract epithelium. Infect Immun. 66:1998;1265-1269.
117. Igietseme J.U., Perry L.L., Ananaba G.A., Uriri I.M., Ojior O., Kumar S.N., Caldwell H.D. Chlamydial infection in inducible nitric oxide synthase knockout mice. Infect Immun. 66:1998;1282-1286.
118. Rottenberg M.E., Rothfuchs A.C.G., Gigliotti D., Svanholm C., Bandholtz L., Wigzell H. Role of innate and adaptive immunity in the outcome of primary infection with Chlamydia pneumoniae, as analyzed in genetically modified mice. J Immunol. 162:1999;2829-2836.
119. MacMicking J.D., Nathan C., Hom G., Chartrain N., Fletcher D.S., Trumbauer M., Stevens K., Xie Q-W., Sokol K., Hutchinson N.et al. Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell. 81:1995;641-650.
120. MacMicking J.D., North R.J., LaCourse R., Mudgett J.S., Shah S.K., Nathan C.F. Identification of nitric oxide synthase as a protective locus against tuberculosis. Proc Natl Acad Sci USA. 94:1997;5243-5248.
121. Doherty T.M., Sher A. Defects in cell-mediated immunity affect chronic, but not innate resistance of mice to Mycobacterium avium infection. J Immunol. 158:1997;4822-4831.
122. Gomes M.S., Florido M., Pais T.F., Appelberg R. Improved clearance of Mycobacterium avium upon disruption of the inducible nitric oxide synthase gene. J Immunol. 162:1999;6734-6739.
123. Way S.S., Goldberg M.B. Clearance of Shigella flexneri infection occurs through a nitric oxide-independent mechanism. Infect Immun. 66:1998;3012-3016.
124. McInnes I.B., Leung B., Wei X-Q., Gemmell C.C., Liew F.Y. Septic arthritis following Staphylococcus aureus infection in mice lacking inducible nitric oxide synthase. J Immunol. 160:1998;308-315.
125. phox-derived ROIs, although participating in the initial control of L. donovani, are dispensable for the ultimate control of the parasites.
126. Favre N., Ryffel B., Rudin W. The development of murine cerebral malaria does not require nitric oxide production. Parasitology. 118:1999;135-138.
127. Yoneto T., Yoshimoto T., Wang C-R., Takahama Y., Tsuji M., Waki S., Nariuchi H. Gamma interferon production is critical for protective immunity to infection with blood-stage Plasmodium berghei XAT but neither NO production nor NK cell activation is critical. Infect Immun. 67:1999;2349-2356.
128. Hölscher C., Köhler G., Müller U., Mossmann H., Schaub G.A., Brombacher F. Defective nitric oxide effector functions lead to extreme susceptibility of Trypanosoma cruzi-infected mice deficient in gamma interferon receptor or inducible nitric oxide synthase. Infect Immun. 66:1998;1208-1215.
129. Millar A.E., Sternberg J., McSharry C., Wei X-Q., Liew F.Y., Turner M.R. T cell responses during Trypanosoma brucei infections in mice deficient in inducible nitric oxide synthase. Infect Immun. 67:1999;3334-3338.
130. Hertz C.J., Mansfield J.M. IFN-γ-dependent nitric oxide production is not linked to resistance in experimental african trypanosomiasis. Cell Immunol. 192:1999;24-32.
131. Scharton-Kersten T.M., Yap G., Magram J., Sher A. Inducible nitric oxide is essential for host control of persistent but not acute infection with the intracellular pathogen Toxoplasma gondii. J Exp Med. 185:1997;1261-1273.
132. Khan I.A., Schwartzman J.D., Matsuura T., Kasper L.H. A dichotomous role for nitric oxide during acute Toxoplasma gondii infection in mice. Proc Natl Acad Sci USA. 94:1997;13955-13960.
133. James S.L., Cheever A.W., Caspar P., Wynn T.A. Inducible nitric oxide synthase-deficient mice develop enhanced type 1 cytokine-associated cellular and humoral immune responses after vaccination with attenuated Schistosoma mansoni cercariae but display partially reduced resistance. Infect Immun. 66:1998;3510-3518.
134. Coulson P.S., Smythies L.E., Betts C., Mabbott N.A., Sternberg J.M., Wei X-G., Liew F.Y. Nitric oxide produced in the lungs of mice immunized with the radiation-attenuated schistosome vaccine is not the major agent casuing challenge parasite elimination. Immunology. 93:1998;55-63.
135. Jackson S.H., Gallin J.I., Holland S.M. The p47phox mouse knock-out model of chronic granulomatous disease. J Exp Med. 182:1995;751-758.
136. Endres R., Luz A., Schulze H., Neubauer H., Fütterer A., Holland
137. Pollock J.D., Williams D.A., Gifford M.A., Li L.L., Du X., Fisherman J., Orkin S.H., Doerschuk C.M., Dinauer M.C. Mouse model of X-linked chronic granulomatous disease, an inherited defect in phagocyte superoxide production. Nat Genet. 9:1995;202-209.
138. Dinauer M.C., Deck M.B., Unanue E.R. Mice lacking reduced nicotinamide adenine dinucleotide phosphate oxidase activity show increased susceptibility to early infection with Listeria monocytogenes. J Immunol. 158:1997;5581-5583.
139. Roberts A.W., Kim C., Zhen L., Lowe J.B., Kapur R., Petryniak B., Spaetti A., Pollock J.D., Borneo J.B., Bradford G.B.et al. Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. Immunity. 10:1999;183-196.