Nitric oxide synthase in innate and adaptive immunity: An update

Trends in Immunology

Volumn 36, Issue 3, 2015, Pages 161-178

  Bogdan, Christian ^a  

^a UNIVERSITY HOSPITAL ERLANGEN   (Germany)

Author keywords

Antimicrobial activity; B cells; Microenvironment; Myeloid cells; Nitric oxide synthases (NOS1 nNOS; NOS2 iNOS; NOS3 eNOS); Th17 cells

Indexed keywords

ALPHA INTERFERON; ARGININE; BETA INTERFERON; COMPLEMENTARY RNA; CYTOKINE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; ERYTHROPOIETIN; GAMMA INTERFERON; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; NEURONAL NITRIC OXIDE SYNTHASE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; NITROGEN; NITROUS OXIDE; S NITROSOTHIOL; SUPPRESSOR OF CYTOKINE SIGNALING 1; UNTRANSLATED RNA; INTERFERON REGULATORY FACTOR 9; IRF9 PROTEIN, HUMAN; ISOENZYME; NOS2 PROTEIN, HUMAN; STAT PROTEIN;

ADAPTIVE IMMUNITY; ANTIBACTERIAL ACTIVITY; ANTIVIRAL ACTIVITY; B LYMPHOCYTE; B LYMPHOCYTE DIFFERENTIATION; BONE MARROW CELL; CELL SURVIVAL; HOST RESISTANCE; HUMAN; INNATE IMMUNITY; LYMPHOCYTE DIFFERENTIATION; MACROPHAGE ACTIVATION; MESENCHYME CELL; NONHUMAN; PLASMA CELL; PROTEIN EXPRESSION; REVIEW; RNA TRANSLATION; SIGNAL TRANSDUCTION; T LYMPHOCYTE; BACTERIUM; BIOSYNTHESIS; GENE EXPRESSION REGULATION; GENETICS; IMMUNOLOGY; LYMPHOCYTE; MACROPHAGE; NEOPLASM; PATHOLOGY;

ADAPTIVE IMMUNITY; BACTERIA; GENE EXPRESSION REGULATION; HUMANS; IMMUNITY, INNATE; INTERFERON-STIMULATED GENE FACTOR 3, GAMMA SUBUNIT; ISOENZYMES; LYMPHOCYTES; MACROPHAGE ACTIVATION; MACROPHAGES; NEOPLASMS; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE II; SIGNAL TRANSDUCTION; STAT TRANSCRIPTION FACTORS;

EID: 84924228289     PISSN: 14714906     EISSN: 14714981     Source Type: Journal    
DOI: 10.1016/j.it.2015.01.003     Document Type: Review

References (257)

1. Stuehr D.J., Marletta M.A. Mammalian nitrite biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide. Proc. Natl. Acad. Sci. U.S.A. 1985, 82:7738-7742.
2. Stuehr D.J., Marletta M.A. Induction of nitrite/nitrate synthesis in murine macrophages by BCG infection, lymphokines or interferon-γ. J. Immunol. 1987, 139:518-525.
3. Hibbs J.B., et al. L-arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells. J. Immunol. 1987, 138:550-565.
4. Hibbs J.B., et al. Macrophage cytotoxicity: role of L-arginine deiminase and imino nitrogen oxidation to nitrite. Science 1987, 235:473-476.
5. Xie Q-W., et al. Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science 1992, 256:225-228.
6. Lowenstein C.J., et al. Cloned and expressed macrophage nitric oxide synthase contrasts with the brain synthase. Proc. Natl. Acad. Sci. U.S.A. 1992, 89:6711-6715.
7. Connor J.R., et al. Suppression of adjuvant-induced arthritis by selective inhibition of inducible nitric oxide synthase. Eur. J. Pharmacol. 1995, 273:15-24.
8. Stenger S., et al. L-N6-(1-iminoethyl)lysine potently inhibits inducible nitric oxide synthase and is superior to NG-monomethyl-arginine in vitro and in vivo. Eur. J. Pharmacol. 1995, 294:703-712.
9. MacMicking J.D., et al. Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell 1995, 81:641-650.
10. Laubach V.E., et al. Mice lacking inducible nitric oxide synthase are not resistant to lipopolysaccharide-induced death. Proc. Natl. Acad. Sci. U.S.A. 1995, 92:10688-10692.
11. Wei X-Q., et al. Altered immune responses in mice lacking inducible nitric oxide synthase. Nature 1995, 375:408-411.
12. Niedbala W., et al. Effects of nitric oxide on the induction and differentiation of Th1 cells. Eur. J. Immunol. 1999, 29:2498-2505.
13. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992, 6:3051-3064.
14. Bogdan C. The function of nitric oxide in the immune system. Handbook of Experimental Pharmacology: Nitric Oxide 2000, 443-492. Springer. B. Mayer (Ed.).
15. Bogdan C. Nitric oxide and the immune response. Nat. Immunol. 2001, 2:907-916.
16. Nathan C. Specificity of a third kind: reactive oxygen and nitrogen intermediates in cell signaling. J. Clin. Invest. 2003, 111:769-778.
17. Bogdan C. Regulation of lymphocytes by nitric oxide. Methods Mol. Biol. 2011, 677:375-393.
18. Wink D.A., et al. Nitric oxide and redox mechanisms in the immune response. J. Leukoc. Biol. 2011, 89:873-891.
19. Bogdan C. Reactive oxygen and reactive nitrogen intermediates in the immune system. The Immune Response to Infection 2011, 69-84. ASM Press. S.H.E. Kaufmann (Ed.).
20. Vodovotz Y., et al. Vesicle membrane association of nitric oxide synthase in primary mouuse macrophages. J. Immunol. 1995, 154:2914-2925.
21. Webb J.L., et al. Macrophage nitric oxide synthase associates with cortical actin but is not recruited to phagosomes. Infect. Immun. 2001, 69:6391-6400.
22. Rahat M.A., et al. Molecular mechanisms regulating macrophage response to hypoxia. Front. Immunol. 2011, 2:45.
23. Thom S.R., et al. Nitric-oxide synthase-2 linkage to focal adhesion kinase in neutrophils influences enzyme activity and beta2 integrin function. J. Biol. Chem. 2013, 288:4810-4818.
24. Glynne P.A., et al. Epithelial inducible nitric-oxide synthase is an apical EBP50-binding protein that directs vectorial nitric oxide output. J. Biol. Chem. 2002, 277:33132-33138.
25. Jyoti A., et al. Interaction of inducible nitric oxide synthase with rac2 regulates reactive oxygen and nitrogen species generation in the human neutrophil phagosomes: implication in microbial killing. Antioxid. Redox Signal. 2014, 20:417-431.
26. Zhang Y., et al. Kinase suppressor of Ras-1 protects against pulmonary Pseudomonas aeruginosa infections. Nat. Med. 2011, 17:341-346.
27. Pandit L., et al. The physiologic aggresome mediates cellular inactivation of iNOS. Proc. Natl. Acad. Sci. U.S.A. 2009, 106:1211-1215.
28. Saini R., et al. Nitric oxide synthase localization in the rat neutrophils: immunocytochemical, molecular, and biochemical studies. J. Leukoc. Biol. 2006, 79:519-528.
29. Chakrabarti S., et al. Neuronal nitric oxide synthase regulates endothelial inflammation. J. Leukoc. Biol. 2012, 91:947-956.
30. Förstermann U., et al. Expressional control of the 'constitutive' isoforms of nitric oxide synthase (NOSI and NOSIII). FASEB J. 1998, 12:773-790.
31. Iwase K., et al. Induction of endothelial nitric oxide synthase in rat brain astrocytes by systemic lipopolysaccharide treatment. J. Biol. Chem. 2000, 275:11929-11933.
32. Boissel J.P., et al. The neuronal nitric oxide synthase is upregulated in mouse skin repair and in response to epidermal growth factor in human HaCaT keratinocytes. J. Invest. Dermatol. 2004, 123:132-139.
33. Dudzinski D.M., et al. The regulation and pharmacology of endothelial nitric oxide synthase. Annu. Rev. Pharmacol. Toxicol. 2006, 46:235-276.
34. Wahl S.M., et al. Nitric oxide in experimental joint inflammation. Benefit or detriment?. Cells Tissues Organs 2003, 174:26-33.
35. Connelly L., et al. Resistance to endotoxic shock in endothelial nitric-oxide synthase (eNOS) knock-out mice: a pro-inflammatory role for eNOS-derived no in vivo. J. Biol. Chem. 2005, 280:10040-10046.
36. Li E., et al. Neuronal nitric oxide synthase is necessary for elimination of Giardia lamblia infections in mice. J. Immunol. 2006, 176:516-521.
37. Martinelli R., et al. ICAM-1-mediated endothelial nitric oxide synthase activation via calcium and AMP-activated protein kinase is required for transendothelial lymphocyte migration. Mol. Biol. Cell 2009, 20:995-1005.
38. Adler H.S., et al. Neuronal nitric oxide synthase modulates maturation of human dendritic cells. J. Immunol. 2010, 184:6025-6034.
39. Fritzsche C., et al. Endothelial nitric oxide synthase limits the inflammatory response in mouse cutaneous leishmaniasis. Immunobiology 2010, 215:826-832.
40. Liao S., et al. Impaired lymphatic contraction associated with immunosuppression. Proc. Natl. Acad. Sci. U.S.A. 2011, 108:18784-18789.
41. Duma D., et al. NOS-1-derived NO is an essential triggering signal for the development of systemic inflammatory responses. Eur. J. Pharmacol. 2011, 668:285-292.
42. Forstermann U., Sessa W.C. Nitric oxide synthases: regulation and function. Eur. Heart J. 2012, 33:829-837.
43. Liu G., et al. ICAM-1-activated Src and eNOS signaling increase endothelial cell surface PECAM-1 adhesivity and neutrophil transmigration. Blood 2012, 120:1942-1952.
44. Huang Z., et al. Stimulation of unprimed macrophages with immune complexes triggers a low output of nitric oxide by calcium-dependent neuronal nitric-oxide synthase. J. Biol. Chem. 2012, 287:4492-4502.
45. Sellers S.L., et al. Nitric oxide and TNFalpha are critical regulators of reversible lymph node vascular remodeling and adaptive immune response. PLoS ONE 2013, 8:e60741.
46. Lundberg J.O., et al. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat. Rev. Drug Discov. 2008, 7:156-167.
47. Doyle M.P., et al. Kinetics and mechanism of the oxidation of human deoxyhemoglobin by nitrites. J. Biol. Chem. 1981, 256:12393-12398.
48. Li H., et al. Nitric oxide production from nitrite occurs primarily in tissues not in the blood: critical role of xanthine oxidase and aldehyde oxidase. J. Biol. Chem. 2008, 283:17855-17863.
49. 2S. Angew. Chem. Int. Ed. Engl. 2013, 52:12061-12064.
50. Oplander C., et al. Mechanism and biological relevance of blue-light (420-453nm)-induced nonenzymatic nitric oxide generation from photolabile nitric oxide derivates in human skin in vitro and in vivo. Free Radic. Biol. Med. 2013, 65:1363-1377.
51. Oplander C., Suschek C.V. The role of photolabile dermal nitric oxide derivates in ultraviolet radiation (UVR)-induced cell death. Int. J. Mol. Sci. 2012, 14:191-204.
52. Liu D., et al. UVA irradiation of human skin vasodilates arterial vasculature and lowers blood pressure independently of nitric oxide synthase. J. Invest. Dermatol. 2014, 134:1839-1846.
53. Kraft B., et al. Microbial nitrate respiration - genes, enzymes and environmental distribution. J. Biotechnol. 2011, 155:104-117.
54. Crane B.R., et al. Bacterial nitric oxide synthases. Annu. Rev. Biochem. 2010, 79:445-470.
55. Anand P., Stamler J.S. Enzymatic mechanisms regulating protein S-nitrosylation: implications in health and disease. J. Mol. Med. (Berl.) 2012, 90:233-244.
56. Radi R. Peroxynitrite, a stealthy biological oxidant. J. Biol. Chem. 2013, 288:26464-26472.
57. Vanin A.F. Dinitrosyl iron complexes with thiolate ligands: physico-chemistry, biochemistry and physiology. Nitric Oxide 2009, 21:1-13.
58. Kroncke K.D., Klotz L.O. Zinc fingers as biologic redox switches?. Antioxid. Redox Signal. 2009, 11:1015-1027.
59. Sawa T., Ohshima H. Nitrative DNA damage in inflammation and its possible role in carcinogenesis. Nitric Oxide 2006, 14:91-100.
60. Jones L.H. Chemistry and biology of biomolecule nitration. Chem. Biol. 2012, 19:1086-1092.
61. Bogdan C. Nitric oxide and the regulation of gene expression. Trends Cell Biol. 2001, 11:66-75.
62. Gould N., et al. Regulation of protein function and signaling by reversible cysteine S-nitrosylation. J. Biol. Chem. 2013, 288:26473-26479.
63. Hernansanz-Agustin P., et al. Nitrosothiols in the immune system: signaling and protection. Antioxid. Redox Signal. 2013, 18:288-308.
64. Lee Y.I., et al. Protein microarray characterization of the S-nitrosoproteome. Mol. Cell. Proteomics 2014, 13:63-72.
65. Doulias P.T., et al. Nitric oxide regulates mitochondrial fatty acid metabolism through reversible protein S-nitrosylation. Sci. Signal. 2013, 6:rs1.
66. 2S and S-nitrosothiols. J. Am. Chem. Soc. 2012, 134:12016-12027.
67. 2S) with the nitrogen oxides. Free Radic. Biol. Med. 2013, 55:1-7.
68. Wang R. Physiological implications of hydrogen sulfide: a whiff exploration that blossomed. Physiol. Rev. 2012, 92:791-896.
69. Kleinert H., et al. Regulation of the expression of inducible nitric oxide synthase. Eur. J. Pharmacol. 2004, 500:255-266.
70. Gao J.J., et al. 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. 1998, 161:4803-4810.
71. Toshchakov V., et al. TLR4, but not TLR2, mediates IFN-β-induced STAT1αβ-dependent gene expression in macrophages. Nat. Immunol. 2002, 3:392-398.
72. Farlik M., et al. Nonconventional initiation complex assembly by STAT and NF-kappaB transcription factors regulates nitric oxide synthase expression. Immunity 2010, 33:25-34.
73. Wienerroither S., et al. Regulation of NO synthesis, local inflammation, and innate immunity to pathogens by BET family proteins. Mol. Cell. Biol. 2014, 34:415-427.
74. Bogdan C. Reactive oxygen and reactive nitrogen metabolites as effector molecules against infectious pathogens. The Innate Immune Response to Infection 2004, 357-396. ASM Press. S.H.E. Kaufmann (Ed.).
75. Fang F.C., Nathan C.F. Man is not a mouse: reply. J. Leukoc. Biol. 2007, 81:580.
76. Ralph A.P., et al. L-arginine and vitamin D: novel adjunctive immunotherapies in tuberculosis. Trends Microbiol. 2008, 16:336-344.
77. Thomas A.C., Mattila J.T. 'Of mice and men': arginine metabolism in macrophages. Front. Immunol. 2014, 5:479.
78. Ralph A.P., et al. Impaired pulmonary nitric oxide bioavailability in pulmonary tuberculosis: association with disease severity and delayed mycobacterial clearance with treatment. J. Infect. Dis. 2013, 208:616-626.
79. Mattila J.T., et al. Microenvironments in tuberculous granulomas are delineated by distinct populations of macrophage subsets and expression of nitric oxide synthase and arginase isoforms. J. Immunol. 2013, 191:773-784.
80. Wilsmann-Theis D., et al. Generation and functional analysis of human TNF-alpha/iNOS-producing dendritic cells (Tip-DC). Allergy 2013, 68:890-898.
81. Zhang X., et al. Transcriptional basis for hyporesponsiveness of the human inducible nitric oxide synthase gene to lipopolysaccharide/interferon-γ. J. Leukoc. Biol. 1996, 59:575-585.
82. Pautz A., et al. Regulation of the expression of inducible nitric oxide synthase. Nitric Oxide 2010, 23:75-93.
83. Gross T.J., et al. Epigenetic silencing of the human NOS2 gene: rethinking the role of nitric oxide in human macrophage inflammatory responses. J. Immunol. 2014, 192:2326-2338.
84. Saldarriaga O.A., et al. Identification of hamster inducible nitric oxide synthase (iNOS) promoter sequences that influence basal and inducible iNOS expression. J. Leukoc. Biol. 2012, 92:205-218.
85. Lima-Junior D.S., et al. Inflammasome-derived IL-1beta production induces nitric oxide-mediated resistance to Leishmania. Nat. Med. 2013, 19:909-915.
86. Guo Z., et al. miRNA-939 regulates human inducible nitric oxide synthase posttranscriptional gene expression in human hepatocytes. Proc. Natl. Acad. Sci. U.S.A. 2012, 109:5826-5831.
87. Matsui K., et al. Natural antisense transcript stabilizes inducible nitric oxide synthase messenger RNA in rat hepatocytes. Hepatology 2008, 47:686-697.
88. Li C., et al. Interleukin-33 increases antibacterial defense by activation of inducible nitric oxide synthase in skin. PLoS Pathog. 2014, 10:e1003918.
89. Brines M., Cerami A. The receptor that tames the innate immune response. Mol. Med. 2012, 18:486-496.
90. Nairz M., et al. Erythropoietin contrastingly affects bacterial infection and experimental colitis by inhibiting nuclear factor-kappaB-inducible immune pathways. Immunity 2011, 34:61-74.
91. Aoshiba K., et al. Therapeutic effects of erythropoietin in murine models of endotoxin shock. Crit. Care Med. 2009, 37:889-898.
92. Banerjee S., et al. miR-125a-5p regulates differential activation of macrophages and inflammation. J. Biol. Chem. 2013, 288:35428-35436.
93. Wang X., et al. Inducible nitric-oxide synthase expression is regulated by mitogen-activated protein kinase phosphatase-1. J. Biol. Chem. 2009, 284:27123-27134.
94. Yang K., et al. miR-155 suppresses bacterial clearance in Pseudomonas aeruginosa-induced keratitis by targeting Rheb. J. Infect. Dis. 2014, 210:89-98.
95. Huang L., et al. Down-regulation of miR-301a suppresses pro-inflammatory cytokines in Toll-like receptor-triggered macrophages. Immunology 2013, 140:314-322.
96. Dai R., et al. Suppression of LPS-induced Interferon-gamma and nitric oxide in splenic lymphocytes by select estrogen-regulated microRNAs: a novel mechanism of immune modulation. Blood 2008, 112:4591-4597.
97. Xu C., et al. miR-155 regulates immune modulatory properties of mesenchymal stem cells by targeting TAK1-binding protein 2. J. Biol. Chem. 2013, 288:11074-11079.
98. Palmieri D., et al. TNFalpha induces the expression of genes associated with endothelial dysfunction through p38MAPK-mediated down-regulation of miR-149. Biochem. Biophys. Res. Commun. 2014, 443:246-251.
99. Zhu H., et al. NPM-ALK up-regulates iNOS expression through a STAT3/microRNA-26a-dependent mechanism. J. Pathol. 2013, 230:82-94.
100. Perske C., et al. Loss of inducible nitric oxide synthase expression in the mouse renal cell carcinoma cell line RENCA is mediated by microRNA miR-146a. Am. J. Pathol. 2010, 177:2046-2054.
101. Khorkova O., et al. Natural antisense transcripts. Hum. Mol. Genet. 2014, 23:R54-R63.
102. Yoshigai E., et al. Natural antisense transcript-targeted regulation of inducible nitric oxide synthase mRNA levels. Nitric Oxide 2013, 30:9-16.
103. Ho J.J., et al. Active stabilization of human endothelial nitric oxide synthase mRNA by hnRNP E1 protects against antisense RNA and microRNAs. Mol. Cell. Biol. 2013, 33:2029-2046.
104. Korneev S.A., et al. Novel noncoding antisense RNA transcribed from human anti-NOS2A locus is differentially regulated during neuronal differentiation of embryonic stem cells. RNA 2008, 14:2030-2037.
105. Olson N., van der Vliet A. Interactions between nitric oxide and hypoxia-inducible factor signaling pathways in inflammatory disease. Nitric Oxide 2011, 25:125-137.
106. Campbell E.L., et al. Transmigrating neutrophils shape the mucosal microenvironment through localized oxygen depletion to influence resolution of inflammation. Immunity 2014, 40:66-77.
107. Mahnke A., et al. Hypoxia in Leishmania major skin lesions impairs the NO-dependent leishmanicidal activity of macrophages. J. Invest. Dermatol. 2014, 134:2339-2346.
108. Robinson M.A., et al. Oxygen-dependent regulation of nitric oxide production by inducible nitric oxide synthase. Free Radic. Biol. Med. 2011, 51:1952-1965.
109. Jantsch J., et al. Toll-like receptor activation and hypoxia use distinct signaling pathways to stabilize hypoxia-inducible factor 1alpha (HIF1A) and result in differential HIF1A-dependent gene expression. J. Leukoc. Biol. 2011, 90:551-562.
110. Elks P.M., et al. Hypoxia inducible factor signaling modulates susceptibility to mycobacterial infection via a nitric oxide dependent mechanism. PLoS Pathog. 2013, 9:e1003789.
111. Go W.Y., et al. NFAT5/TonEBP mutant mice define osmotic stress as a critical feature of the lymphoid microenvironment. Proc. Natl. Acad. Sci. U.S.A. 2004, 101:10673-10678.
112. Wiig H., et al. Immune cells control skin lymphatic electrolyte homeostasis and blood pressure. J. Clin. Invest. 2013, 123:2803-2815.
113. Shapiro L., Dinarello C.A. Osmotic regulation of cytokine synthesis in vitro. Proc. Natl. Acad. Sci. U.S.A. 1995, 92:12230-12234.
114. + storage strengthens the antimicrobial barrier function of the skin and boosts macrophage-driven host defense. Cell Metab. 2015, (in press).
115. Neuhofer W. Role of NFAT5 in inflammatory disorders associated with osmotic stress. Curr. Genomics 2010, 11:584-590.
116. Buxade M., et al. Gene expression induced by Toll-like receptors in macrophages requires the transcription factor NFAT5. J. Exp. Med. 2012, 209:379-393.
117. Lee M., Choy J.C. Positive feedback regulation of human inducible nitric-oxide synthase expression by Ras protein S-nitrosylation. J. Biol. Chem. 2013, 288:15677-15686.
118. Mundy-Bosse B.L., et al. Myeloid-derived suppressor cell inhibition of the IFN response in tumor-bearing mice. Cancer Res. 2011, 71:5101-5110.
119. Kolluru G.K., et al. Hydrogen sulfide chemical biology: pathophysiological roles and detection. Nitric Oxide 2013, 35:5-20.
120. Altaany Z., et al. The coordination of S-sulfhydration, S-nitrosylation, and phosphorylation of endothelial nitric oxide synthase by hydrogen sulfide. Sci. Signal. 2014, 7:ra87.
121. Oh G.S., et al. Hydrogen sulfide inhibits nitric oxide production and nuclear factor-kappaB via heme oxygenase-1 expression in RAW264.7 macrophages stimulated with lipopolysaccharide. Free Radic. Biol. Med. 2006, 41:106-119.
122. Badiei A., et al. Inhibition of hydrogen sulfide production by gene silencing attenuates inflammatory activity of LPS-activated RAW264.7 cells. Appl. Microbiol. Biotechnol. 2013, 97:7845-7852.
123. Gozzelino R., et al. Mechanisms of cell protection by heme oxygenase-1. Annu. Rev. Pharmacol. Toxicol. 2010, 50:323-354.
124. Fourquet S., et al. Activation of NRF2 by nitrosative agents and H2O2 involves KEAP1 disulfide formation. J. Biol. Chem. 2010, 285:8463-8471.
125. Sarady J.K., et al. Carbon monoxide protection against endotoxic shock involves reciprocal effects on iNOS in the lung and liver. FASEB J. 2004, 18:854-856.
126. Vareille M., et al. Heme oxygenase-1 is a critical regulator of nitric oxide production in enterohemorrhagic Escherichia coli-infected human enterocytes. J. Immunol. 2008, 180:5720-5726.
127. Nairz M., et al. Iron at the interface of immunity and infection. Front. Pharmacol. 2014, 5:152.
128. Tzima S., et al. Myeloid heme oxygenase-1 regulates innate immunity and autoimmunity by modulating IFN-beta production. J. Exp. Med. 2009, 206:1167-1179.
129. Jais A., et al. Heme oxygenase-1 drives metaflammation and insulin resistance in mouse and man. Cell 2014, 158:25-40.
130. Daniliuc S., et al. Hypoxia inactivates inducible nitric oxide synthase in mouse macrophages by disrupting its interaction with alpha-actinin 4. J. Immunol. 2003, 171:3225-3232.
131. Zhang W., et al. Protein-protein interactions involving inducible nitric oxide synthase. Acta Physiol. Scand. 2003, 179:137-142.
132. Yoshida M., Xia Y. Heat shock protein 90 as an endogenous protein enhancer of inducible nitric-oxide synthase. J. Biol. Chem. 2003, 278:36953-36958.
133. Davis A.S., et al. Mechanism of inducible nitric oxide synthase exclusion from mycobacterial phagosomes. PLOS Pathog. 2007, 3:1887-1894.
134. Mazumdar T., et al. Regulation of NF-kappaB activity and inducible nitric oxide synthase by regulatory particle non-ATPase subunit 13 (Rpn13). Proc. Natl. Acad. Sci. U.S.A. 2010, 107:13854-13859.
135. Hadkar V., et al. Carboxypeptidase-mediated enhancement of nitric oxide production in rat lungs and microvascular endothelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 2004, 287:L35-L45.
136. Goto Y., et al. Substrate-dependent nitric oxide synthesis by secreted endoplasmic reticulum aminopeptidase 1 in macrophages. J. Biochem. 2015, Published online January 9, 2015. http://dx.doi.org/10.1093/jb/mvv001.
137. Morris S.M. Recent advances in arginine metabolism: roles and regulation of the arginases. Br. J. Pharmacol. 2009, 157:922-930.
138. Michel T. R is for arginine: metabolism of arginine takes off again, in new directions. Circulation 2013, 128:1400-1404.
139. El Kasmi K.C., et al. Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens. Nat. Immunol. 2008, 9:1399-1406.
140. König T., et al. Translational repression of inducible NO synthase in macrophages by L-arginine depletion is not associated with an increased phosphorylation of eIF2alpha. Immunobiology 2009, 214:822-827.
141. Duque-Correa M.A., et al. Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas. Proc. Natl. Acad. Sci. U.S.A. 2014, 111:E4024-E4032.
142. Elms S., et al. Insights into the arginine paradox: evidence against the importance of subcellular location of arginase and eNOS. Am. J. Physiol. Heart Circ. Physiol. 2013, 305:H651-H666.
143. Qualls J.E., et al. Sustained generation of nitric oxide and control of mycobacterial infection requires argininosuccinate synthase 1. Cell Host Microbe 2012, 12:313-323.
144. Wijnands K.A., et al. Citrulline a more suitable substrate than arginine to restore NO production and the microcirculation during endotoxemia. PLoS ONE 2012, 7:e37439.
145. Grady S.L., et al. Argininosuccinate synthetase 1 depletion produces a metabolic state conducive to herpes simplex virus 1 infection. Proc. Natl. Acad. Sci. U.S.A. 2013, 110:E5006-E5015.
146. Wu G., et al. Arginine metabolism and nutrition in growth, health and disease. Amino Acids 2009, 37:153-168.
147. Stadelmann B., et al. The role of arginine and arginine-metabolizing enzymes during Giardia-host cell interactions in vitro. BMC Microbiol. 2013, 13:256.
148. Regunathan S., Piletz J.E. Regulation of inducible nitric oxide synthase and agmatine synthesis in macrophages and astrocytes. Ann. N. Y. Acad. Sci. 2003, 1009:20-29.
149. Molderings G.J., Haenisch B. Agmatine (decarboxylated L-arginine): physiological role and therapeutic potential. Pharmacol. Ther. 2012, 133:351-365.
150. Deeb R.S., et al. Characterization of a cellular denitrase activity that reverses nitration of cyclooxygenase. Am. J. Physiol. Heart Circ. Physiol. 2013, 305:H687-H698.
151. Nathan C., Shiloh M.U. Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc. Natl. Acad. Sci. U.S.A. 2000, 97:8841-8848.
152. Fang F.C. Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nat. Rev. Immunol. 2004, 2:820-832.
153. Feng H.M., Walker D.H. Mechanisms of intracellular killing of Rickettsia conorii in infected human endothelial cells, hepatocytes, and macrophages. Infect. Immun. 2000, 68:6729-6736.
154. Serbina N.V., et al. TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity 2003, 19:59-70.
155. Copin R., et al. In situ microscopy analysis reveals local innate immune response developed around Brucella infected cells in resistant and susceptible mice. PLoS Pathog. 2012, 8:e1002575.
156. Gebreselassie N.G., et al. Eosinophils preserve parasitic nematode larvae by regulating local immunity. J. Immunol. 2012, 188:417-425.
157. Su Y.C., et al. Dual pro-inflammatory and antiviral properties of pulmonary eosinophils in respiratory syncytial virus (RSV) vaccine-enhanced disease. J. Virol. 2015, 89:1564-1578.
158. Jones-Carson J., et al. Inactivation of [Fe-S] metalloproteins mediates nitric oxide-dependent killing of Burkholderia mallei. PLoS ONE 2008, 3:e1976.
159. Richardson A.R., et al. Multiple targets of nitric oxide in the tricarboxylic acid cycle of Salmonella enterica serovar typhimurium. Cell Host Microbe 2011, 10:33-43.
160. Savidge T.C., et al. Host S-nitrosylation inhibits clostridial small molecule-activated glucosylating toxins. Nat. Med. 2011, 17:1136-1141.
161. Muller A.J., et al. Photoconvertible pathogen labeling reveals nitric oxide control of Leishmania major infection in vivo via dampening of parasite metabolism. Cell Host Microbe 2013, 14:460-467.
162. Burkholder K.M., et al. A small molecule deubiquitinase inhibitor increases localization of inducible nitric oxide synthase to the macrophage phagosome and enhances bacterial killing. Infect. Immun. 2011, 79:4850-4857.
163. Bogdan C., et al. Fibroblasts as host cells in latent leishmaniosis. J. Exp. Med. 2000, 191:2121-2129.
164. Olekhnovitch R., et al. Collective nitric oxide production provides tissue-wide immunity during Leishmania infection. J. Clin. Invest. 2014, 124:1711-1722.
165. Herbst S., et al. Interferon gamma activated macrophages kill mycobacteria by nitric oxide induced apoptosis. PLoS ONE 2011, 6:e19105.
166. Zwaferink H., et al. Stimulation of inducible nitric oxide synthase expression by beta interferon increases necrotic death of macrophages upon Listeria monocytogenes infection. Infect. Immun. 2008, 76:1649-1656.
167. Ito C., et al. Endogenous nitrated nucleotide is a key mediator of autophagy and innate defense against bacteria. Mol. Cell 2013, 52:794-804.
168. Li X., et al. Atg7 enhances host defense against infection via downregulation of superoxide but upregulation of nitric oxide. J. Immunol. 2015, 194:1112-1121.
169. Nairz M., et al. Nitric oxide-mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection. J. Exp. Med. 2013, 210:855-873.
170. Axelrod S., et al. Delay of phagosome maturation by a mycobacterial lipid is reversed by nitric oxide. Cell Microbiol. 2008, 10:1530-1545.
171. Vareille M., et al. Nitric oxide inhibits Shiga-toxin synthesis by enterohemorrhagic Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 2007, 104:10199-10204.
172. Branchu P., et al. NsrR, GadE, and GadX interplay in repressing expression of the Escherichia coli O157:H7 LEE pathogenicity island in response to nitric oxide. PLoS Pathog. 2014, 10:e1003874.
173. Barraud N., et al. Nitric oxide: a key mediator of biofilm dispersal with applications in infectious diseases. Curr. Pharm. Des. 2014, 21:21-42.
174. Ramphul U.N., et al. Plasmodium falciparum evades mosquito immunity by disrupting JNK-mediated apoptosis of invaded midgut cells. Proc. Natl. Acad. Sci. U.S.A. 2014, Published online December 31, 2014. http://dx.doi.org/10.1073/pnas.1423586112.
175. Burton N.A., et al. Disparate impact of oxidative host defenses determines the fate of Salmonella during systemic infection in mice. Cell Host Microbe 2014, 15:72-83.
176. Lu W., et al. Structural and functional characterization of the nitrite channel NirC from Salmonella typhimurium. Proc. Natl. Acad. Sci. U.S.A. 2012, 109:18395-18400.
177. Cole C., et al. Nitric oxide increases susceptibility of Toll-like receptor-activated macrophages to spreading Listeria monocytogenes. Immunity 2012, 36:807-820.
178. Bogdan C. Listeria monocytogenes: no spreading without NO. Immunity 2012, 36:697-699.
179. Shatalin K., et al. Bacillus anthracis-derived nitric oxide is essential for pathogen virulence and survival in macrophages. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:1009-1013.
180. van Sorge N.M., et al. Methicillin-resistant Staphylococcus aureus bacterial nitric-oxide synthase affects antibiotic sensitivity and skin abscess development. J. Biol. Chem. 2013, 288:6417-6426.
181. Brown G.C. Reversible binding and inhibition of catalase by nitric oxide. Eur. J. Biochem. 1995, 232:188-191.
182. Sigfrid L.A., et al. Cytokines and nitric oxide inhibit the enzyme activity of catalase but not its protein or mRNA expression in insulin-producing cells. J. Mol. Endocrinol. 2003, 31:509-518.
183. Karlinsey J.E., et al. The NsrR regulon in nitrosative stress resistance of Salmonella enterica serovar Typhimurium. Mol. Microbiol. 2012, 85:1179-1193.
184. Husain M., et al. Ferric uptake regulator-dependent antinitrosative defenses in Salmonella enterica serovar Typhimurium pathogenesis. Infect. Immun. 2014, 82:333-340.
185. Kinkel T.L., et al. The Staphylococcus aureus SrrAB two-component system promotes resistance to nitrosative stress and hypoxia. MBio 2013, 4. e00696-00613.
186. Lopez C.A., et al. Phage-mediated acquisition of a type III secreted effector protein boosts growth of salmonella by nitrate respiration. MBio 2012, 3:e00143-e212.
187. Winter S.E., et al. Host-derived nitrate boosts growth of E. coli in the inflamed gut. Science 2013, 339:708-711.
188. Spees A.M., et al. Streptomycin-induced inflammation enhances Escherichia coli gut colonization through nitrate respiration. MBio 2013, 4:e00143-e212.
189. Seth D., et al. Endogenous protein S-mitrosylation in E. coli: regulation by OxyR. Science 2012, 336:470-473.
190. Jung J.Y., et al. The intracellular environment of human macrophages that produce nitric oxide promotes growth of mycobacteria. Infect. Immun. 2013, 81:3198-3209.
191. Tan M.P., et al. Nitrate respiration protects hypoxic Mycobacterium tuberculosis against acid- and reactive nitrogen species stresses. PLoS ONE 2010, 5:e13356.
192. Sohaskey C.D. Nitrate enhances the survival of Mycobacterium tuberculosis during inhibition of respiration. J. Bacteriol. 2008, 190:2981-2986.
193. Cunningham-Bussel A., et al. Nitrite produced by Mycobacterium tuberculosis in human macrophages in physiologic oxygen impacts bacterial ATP consumption and gene expression. Proc. Natl. Acad. Sci. U.S.A. 2013, 110:E4256-E4265.
194. Mocca B., Wang W. Bacterium-generated nitric oxide hijacks host tumor necrosis factor alpha signaling and modulates the host cell cycle in vitro. J. Bacteriol. 2012, 194:4059-4068.
195. Das P., et al. Modulation of the arginase pathway in the context of microbial pathogenesis: a metabolic enzyme moonlighting as an immune modulator. PLoS Pathog. 2010, 6:e1000899.
196. Cusumano Z.T., et al. Streptococcus pyogenes arginine and citrulline catabolism promotes infection and modulates innate immunity. Infect. Immun. 2014, 82:233-242.
197. Choi Y., et al. Expression of STM4467-encoded arginine deiminase controlled by the STM4463 regulator contributes to Salmonella enterica serovar Typhimurium virulence. Infect. Immun. 2012, 80:4291-4297.
198. Darlyuk I., et al. Arginine homeostasis and transport in the human pathogen Leishmania donovani. J. Biol. Chem. 2009, 284:19800-19807.
199. Bogdan C. Mechanisms and consequences of persistence of intracellular pathogens: leishmaniasis as an example. Cell. Microbiol. 2008, 10:1221-1234.
200. Brune B., et al. Redox control of inflammation in macrophages. Antioxid. Redox Signal. 2013, 19:595-637.
201. + macrophages in experimental autoimmune myocarditis. Cardiovasc. Res. 2013, 97:219-229.
202. Rigamonti E., et al. Requirement of inducible nitric oxide synthase for skeletal muscle regeneration after acute damage. J. Immunol. 2013, 190:1767-1777.
203. Sarkar S., et al. Complex inhibitory effects of nitric oxide on autophagy. Mol. Cell 2011, 43:19-32.
204. Yang Z., et al. Lymphocyte development requires S-nitrosoglutathione reductase. J. Immunol. 2010, 185:6664-6669.
205. Niedbala W., et al. Nitric oxide-induced regulatory T cells inhibit Th17 but not Th1 cell differentiation and function. J. Immunol. 2013, 191:164-170.
206. Niedbala W., et al. Nitric oxide enhances Th9 cell differentiation and airway inflammation. Nat. Commun. 2014, 5:4575.
207. Yang J., et al. T cell-derived inducible nitric oxide synthase switches off Th17 cell differentiation. J. Exp. Med. 2013, 210:1447-1462.
208. + regulatory T cell differentiation and potentiate Th1 development. J. Immunol. 2011, 186:6972-6980.
209. Obermajer N., et al. Induction and stability of human Th17 cells require endogenous NOS2 and cGMP-dependent NO signaling. J. Exp. Med. 2013, 210:1433-1445.
210. Tumurkhuu G., et al. B1 cells produce nitric oxide in response to a series of toll-like receptor ligands. Cell. Immunol. 2010, 261:122-127.
211. Saini A.S., et al. Inducible nitric oxide synthase is a major intermediate in signaling pathways for the survival of plasma cells. Nat. Immunol. 2014, 15:275-282.
212. Jayasekera J.P., et al. Enhanced antiviral antibody secretion and attenuated immunopathology during influenza virus infection in nitric oxide synthase-2-deficient mice. J. Gen. Virol. 2006, 87:3361-3371.
213. Tezuka H., et al. Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells. Nature 2007, 448:929-933.
214. Giordano D., et al. Nitric oxide regulates BAFF expression and T cell-independent antibody responses. J. Immunol. 2014, 193:1110-1120.
215. Ren G., et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2008, 2:141-150.
216. Shi Y., et al. How mesenchymal stem cells interact with tissue immune responses. Trends Immunol. 2012, 33:136-143.
217. Lukacs-Kornek V., et al. Regulated release of nitric oxide by nonhematopoietic stroma controls expansion of the activated T cell pool in lymph nodes. Nat. Immunol. 2011, 12:1096-1104.
218. Siegert S., et al. Fibroblastic reticular cells from lymph nodes attenuate T cell expansion by producing nitric oxide. PLoS ONE 2011, 6:e27618.
219. Scallan J.P., Davis M.J. Genetic removal of basal nitric oxide enhances contractile activity in isolated murine collecting lymphatic vessels. J. Physiol. 2013, 591:2139-2156.
220. Chandrasekar B., et al. Regulation of chemokines, CCL3 and CCL4, by interferon gamma and nitric oxide synthase 2 in mouse macrophages and during Salmonella enterica serovar typhimurium infection. J. Infect. Dis. 2013, 207:1556-1568.
221. Molon B., et al. Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells. J. Exp. Med. 2011, 208:1949-1962.
222. Norman M.U., et al. Interferon-gamma limits Th1 lymphocyte adhesion to inflamed endothelium: a nitric oxide regulatory feedback mechanism. Eur. J. Immunol. 2008, 38:1368-1380.
223. + DC subset that regulates Th1 immune responses. J. Leukoc. Biol. 2011, 89:443-455.
224. Hernandez-Cuellar E., et al. Cutting edge: nitric oxide inhibits the NLRP3 inflammasome. J. Immunol. 2012, 189:5113-5117.
225. Mishra B.B., et al. Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome-dependent processing of IL-1beta. Nat. Immunol. 2013, 14:52-60.
226. Mao K., et al. Nitric oxide suppresses NLRP3 inflammasome activation and protects against LPS-induced septic shock. Cell Res. 2013, 23:201-212.
227. + T effectors: selective regulation of T effector-memory apoptosis by inducible nitric oxide synthase. J. Immunol. 2013, 190:97-105.
228. Bogdan C. The multiplex function of nitric oxide in (auto)immunity. J. Exp. Med. 1998, 187:1361-1365.
229. Burke A.J., et al. The yin and yang of nitric oxide in cancer progression. Carcinogenesis 2013, 34:503-512.
230. Schairer D.O., et al. The potential of nitric oxide releasing therapies as antimicrobial agents. Virulence 2012, 3:271-279.
231. Hauser B., et al. Nitric oxide synthase inhibition in sepsis? Lessons learned from large-animal studies. Anesth. Analg. 2005, 101:488-498.
232. Fletcher A.L., et al. Lymph node fibroblastic reticular cell transplants show robust therapeutic efficacy in high-mortality murine sepsis. Sci. Transl. Med. 2014, 6:249ra109.
233. Beury D.W., et al. Cross-talk among myeloid-derived suppressor cells, macrophages, and tumor cells impacts the inflammatory milieu of solid tumors. J. Leukoc. Biol. 2014, 96:1109-1118.
234. Weigert A., Brune B. Nitric oxide, apoptosis and macrophage polarization during tumor progression. Nitric Oxide 2008, 19:95-102.
235. Gabrilovich D.I., et al. Coordinated regulation of myeloid cells by tumours. Nat. Rev. Immunol. 2012, 12:253-268.
236. Heinecke J.L., et al. Tumor microenvironment-based feed-forward regulation of NOS2 in breast cancer progression. Proc. Natl. Acad. Sci. U.S.A. 2014, 111:6323-6328.
237. Long Y., et al. Arginine deiminase resistance in melanoma cells is associated with metabolic reprogramming, glucose dependence, and glutamine addiction. Mol. Cancer Ther. 2013, 12:2581-2590.
238. Huang H.L., et al. Attenuation of argininosuccinate lyase inhibits cancer growth via cyclin A2 and nitric oxide. Mol. Cancer Ther. 2013, 12:2505-2516.
239. Phillips M.M., et al. Targeting arginine-dependent cancers with arginine-degrading enzymes: opportunities and challenges. Cancer Res. Treat. 2013, 45:251-262.
240. Feun L.G., et al. Arginine deprivation in cancer therapy. Curr. Opin. Clin. Nutr. Metab. Care 2015, 18:78-82.
241. Austin S.A., et al. Endothelial nitric oxide deficiency promotes Alzheimer's disease pathology. J. Neurochem. 2013, 127:691-700.
242. Nathan C., et al. Protection from Alzheimer's-like disease in the mouse by genetic ablation of inducible nitric oxide synthase. J. Exp. Med. 2005, 202:1163-1169.
243. Heneka M.T., et al. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 2013, 493:674-678.
244. Kummer M.P., et al. Nitric oxide decreases the enzymatic activity of insulin degrading enzyme in APP/PS1 mice. J. Neuroimmune Pharmacol. 2012, 7:165-172.
245. Liu P., et al. Altered arginine metabolism in Alzheimer's disease brains. Neurobiol. Aging 2014, 35:1992-2003.
246. Stuehr D.J., et al. Structural and mechanistic aspects of flavoproteins: electron transfer through the nitric oxide synthase flavoprotein domain. FEBS J. 2009, 276:3959-3974.
247. Campbell M.G., et al. Molecular architecture of mammalian nitric oxide synthases. Proc. Natl. Acad. Sci. U.S.A. 2014, 111:E3614-E3623.
248. Smith B.C., Marletta M.A. Mechanisms of S-nitrosothiol formation and selectivity in nitric oxide signaling. Curr. Opin. Chem. Biol. 2012, 16:498-506.
249. Heinrich T.A., et al. Biological nitric oxide signalling: chemistry and terminology. Br. J. Pharmacol. 2013, 169:1417-1429.
250. Motz G.T., Coukos G. Deciphering and reversing tumor immune suppression. Immunity 2013, 39:61-73.
251. Jayaraman P., et al. Tumor-expressed inducible nitric oxide synthase controls induction of functional myeloid-derived suppressor cells through modulation of vascular endothelial growth factor release. J. Immunol. 2012, 188:5365-5376.
252. +/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell 2013, 24:589-602.
253. Eyler C.E., et al. Glioma stem cell proliferation and tumor growth are promoted by nitric oxide synthase-2. Cell 2011, 146:53-66.
254. Weiss J.M., et al. Macrophage-dependent nitric oxide expression regulates tumor cell detachment and metastasis after IL-2/anti-CD40 immunotherapy. J. Exp. Med. 2010, 207:2455-2467.
255. Switzer C.H., et al. S-nitrosylation of EGFR and Src activates an oncogenic signaling network in human basal-like breast cancer. Mol. Cancer Res. 2012, 10:1203-1215.
256. Jeon H.M., et al. Crosstalk between glioma-initiating cells and endothelial cells drives tumor progression. Cancer Res. 2014, 74:4482-4492.
257. Deng M., et al. Shedding of the tumor necrosis factor (TNF) receptor from the surface of hepatocytes during sepsis limits inflammation through cGMP signaling. Sci. Signal. 2015, http://stke.sciencemag.org/content/8/361/ra11.long.