Human monocytes/macrophages: NO or no NO?

M Denis
Pulmonary Research Unit, Faculty of Medicine, University of Sherbrooke, Canada.

The production of nitric oxide (NO) and other reactive nitrogen intermediates by cytokine-activated rodent cells is an important component of antimicrobial and/or antineoplastic activity of these cells. This pathway involves the oxidation of arginine to citrulline, with the concomitant release of NO by an inducible form of NO synthase (iNOS). Numerous cell types express iNOS after stimulation with bacterial products and/or cytokines. The role of NO and its derivatives in host resistance is a subject of intense investigation in mouse models of infections or neoplasia. Although human cells such as hepatocytes and endothelial cells have been shown to express an inducible NO synthase, the presence of such a pathway in human monocytes/macrophages has been questioned by many investigators and is a subject of great controversy. In this short review, we discuss some salient points of this debate.

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				A. Nicolas, D. Cathelin, N. Larmonier, J. Fraszczak, P.-E. Puig, A. Bouchot, A. Bateman, E. Solary, and B. Bonnotte Dendritic Cells Trigger Tumor Cell Death by a Nitric Oxide-Dependent Mechanism J. Immunol., July 15, 2007; 179(2): 812 - 818. [Abstract] [Full Text] [PDF]

				J. Bultinck, P. Sips, L. Vakaet, P. Brouckaert, and A. Cauwels Systemic NO production during (septic) shock depends on parenchymal and not on hematopoietic cells: in vivo iNOS expression pattern in (septic) shock FASEB J, November 1, 2006; 20(13): 2363 - 2365. [Abstract] [Full Text] [PDF]

				L. E. Perez, B. Chandrasekar, O. A. Saldarriaga, W. Zhao, L. T. Arteaga, B. L. Travi, and P. C. Melby Reduced Nitric Oxide Synthase 2 (NOS2) Promoter Activity in the Syrian Hamster Renders the Animal Functionally Deficient in NOS2 Activity and Unable to Control an Intracellular Pathogen J. Immunol., May 1, 2006; 176(9): 5519 - 5528. [Abstract] [Full Text] [PDF]

				A. Jeevan, C. T. McFarland, T. Yoshimura, T. Skwor, H. Cho, T. Lasco, and D. N. McMurray Production and Characterization of Guinea Pig Recombinant Gamma Interferon and Its Effect on Macrophage Activation Infect. Immun., January 1, 2006; 74(1): 213 - 224. [Abstract] [Full Text] [PDF]

				N. Foster, S. Hulme, M. Lovell, K. Reed, and P. Barrow Stimulation of gp91 Phagocytic Oxidase and Reactive Oxygen Species in Neutrophils by an Avirulent Salmonella enterica Serovar Infantis Strain Protects Gnotobiotic Piglets from Lethal Challenge with Serovar Typhimurium Strain F98 without Inducing Intestinal Pathology Infect. Immun., August 1, 2005; 73(8): 4539 - 4547. [Abstract] [Full Text] [PDF]

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				I. Smith Mycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence Clin. Microbiol. Rev., July 1, 2003; 16(3): 463 - 496. [Abstract] [Full Text] [PDF]

				M. Ameen, I. Ahmad, S. Musthapa, M. A. Baig, R. Mishra, and Q. Rahman Differential responses of rat alveolar macrophages to carpet dust in vitro Human and Experimental Toxicology, May 1, 2003; 22(5): 263 - 270. [Abstract] [PDF]

				A. Klegeris and P. L. McGeer Toxicity of human monocytic THP-1 cells and microglia toward SH-SY5Y neuroblastoma cells is reduced by inhibitors of 5-lipoxygenase and its activating protein FLAP J. Leukoc. Biol., March 1, 2003; 73(3): 369 - 378. [Abstract] [Full Text] [PDF]

				S. Blesson, J. Thiery, C. Gaudin, R. Stancou, J.-P. Kolb, J.-L. Moreau, J. Theze, F. Mami-Chouaib, and S. Chouaib Analysis of the mechanisms of human cytotoxic T lymphocyte response inhibition by NO Int. Immunol., October 1, 2002; 14(10): 1169 - 1178. [Abstract] [Full Text] [PDF]

				S. Kim and P. Ponka Nitrogen monoxide-mediated control of ferritin synthesis: Implications for macrophage iron homeostasis PNAS, September 17, 2002; 99(19): 12214 - 12219. [Abstract] [Full Text] [PDF]

				D. G. Alleva, E. B Johnson, F. M Lio, S. A Boehme, P. J Conlon, and P. D. Crowe Regulation of murine macrophage proinflammatory and anti-inflammatory cytokines by ligands for peroxisome proliferator-activated receptor-{gamma}: counter-regulatory activity by IFN-{gamma} J. Leukoc. Biol., April 1, 2002; 71(4): 677 - 685. [Abstract] [Full Text] [PDF]

				H. Pfister, K. A. Remer, M. Brcic, R. Fatzer, S. Christen, S. Leib, and T. W. Jungi Inducible Nitric Oxide Synthase and Nitrotyrosine in Listeric Encephalitis: A Cross-species Study in Ruminants Veterinary Pathology, March 1, 2002; 39(2): 190 - 199. [Abstract] [Full Text] [PDF]

				P. Dickie, A. Roberts, and R. Lee A defect in HIV-1 transgenic murine macrophages results in deficient nitric oxide production J. Leukoc. Biol., October 1, 2001; 70(4): 592 - 600. [Abstract] [Full Text] [PDF]

				M. Lehner, T. Felzmann, K. Clodi, and W. Holter Type I interferons in combination with bacterial stimuli induce apoptosis of monocyte-derived dendritic cells Blood, August 1, 2001; 98(3): 736 - 742. [Abstract] [Full Text] [PDF]

				K. A. Remer, T. W. Jungi, R. Fatzer, M. G. Tauber, and S. L. Leib Nitric Oxide Is Protective in Listeric Meningoencephalitis of Rats Infect. Immun., June 1, 2001; 69(6): 4086 - 4093. [Abstract] [Full Text] [PDF]

				M. Hori, M. Kita, S. Torihashi, S. Miyamoto, K.-J. Won, K. Sato, H. Ozaki, and H. Karaki Upregulation of iNOS by COX-2 in muscularis resident macrophage of rat intestine stimulated with LPS Am J Physiol Gastrointest Liver Physiol, May 1, 2001; 280(5): G930 - G938. [Abstract] [Full Text] [PDF]

				K. H. N. Hoebe, R. F. Witkamp, J. Fink-Gremmels, A. S. J. P. A. M. Van Miert, and M. Monshouwer Direct cell-to-cell contact between Kupffer cells and hepatocytes augments endotoxin-induced hepatic injury Am J Physiol Gastrointest Liver Physiol, April 1, 2001; 280(4): G720 - G728. [Abstract] [Full Text] [PDF]

JOURNAL ARTICLE

Human monocytes/macrophages: NO or no NO?

				S. ZHU, L. B. WARE, T. GEISER, M. A. MATTHAY, and S. MATALON Increased Levels of Nitrate and Surfactant Protein A Nitration in the Pulmonary Edema Fluid of Patients with Acute Lung Injury Am. J. Respir. Crit. Care Med., January 1, 2001; 163(1): 166 - 172. [Abstract] [Full Text]

				S Schweyer, S Mihm, H J Radzun, H Hartmann, and A Fayyazi Liver infiltrating T lymphocytes express interferon gamma and inducible nitric oxide synthase in chronic hepatitis C virus infection Gut, February 1, 2000; 46(2): 255 - 259. [Abstract] [Full Text] [PDF]

				L. Comini, T. Bachetti, L. Agnoletti, G. Gaia, S. Curello, B. Milanesi, M. Volterrani, G. Parrinello, C. Ceconi, A. Giordano, et al. Induction of functional inducible nitric oxide synthase in monocytes of patients with congestive heart failure. Link with tumour necrosis factor-{alpha} Eur. Heart J., October 2, 1999; 20(20): 1503 - 1513. [Abstract] [PDF]

				D. Burgner, K. Rockett, and D. Kwiatkowski Nitric oxide and infectious diseases Arch. Dis. Child., August 1, 1999; 81(2): 185 - 188. [Full Text]

				P. Ekman, M. Saarinen, Q. He, M. Virtala, M. Salmi, and K. Granfors Human Monocytic U937 Cells Kill Salmonella In Vitro by NO-Independent Mechanisms Infect. Immun., July 1, 1999; 67(7): 3670 - 3673. [Abstract] [Full Text] [PDF]

				D. W. Mullins, C. J. Burger, and K. D. Elgert Paclitaxel Enhances Macrophage IL-12 Production in Tumor-Bearing Hosts Through Nitric Oxide J. Immunol., June 1, 1999; 162(11): 6811 - 6818. [Abstract] [Full Text] [PDF]

				K. Hori, P. R. Burd, K. Furuke, J. Kutza, K. A. Weih, and K. A. Clouse Human Immunodeficiency Virus-1-Infected Macrophages Induce Inducible Nitric Oxide Synthase and Nitric Oxide (NO) Production in Astrocytes: Astrocytic NO as a Possible Mediator of Neural Damage in Acquired Immunodeficiency Syndrome Blood, March 15, 1999; 93(6): 1843 - 1850. [Abstract] [Full Text] [PDF]

				F. Facchetti, W. Vermi, S. Fiorentini, M. Chilosi, A. Caruso, M. Duse, L. D. Notarangelo, and R. Badolato Expression of Inducible Nitric Oxide Synthase in Human Granulomas and Histiocytic Reactions Am. J. Pathol., January 1, 1999; 154(1): 145 - 152. [Abstract] [Full Text] [PDF]

				K. A. Rockett, R. Brookes, I. Udalova, V. Vidal, A. V.�S. Hill, and D. Kwiatkowski 1,25-Dihydroxyvitamin D3 Induces Nitric Oxide Synthase and Suppresses Growth of Mycobacterium tuberculosis in a Human Macrophage-Like Cell Line Infect. Immun., November 1, 1998; 66(11): 5314 - 5321. [Abstract] [Full Text] [PDF]

				M. B. Hampton, A. J. Kettle, and C. C. Winterbourn Inside the Neutrophil Phagosome: Oxidants, Myeloperoxidase, and Bacterial Killing Blood, November 1, 1998; 92(9): 3007 - 3017. [Full Text] [PDF]