The DOI matches its Crossref record; 104 of the 105 references it cites were found in a registry or an index.
Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens
Open accessAbstract
This review summarizes recent evidence from knock-out mice on the role of reactive oxygen intermediates and reactive nitrogen intermediates (RNI) in mammalian immunity. Reflections on redundancy in immunity help explain an apparent paradox: the phagocyte oxidase and inducible nitric oxide synthase are each nonredundant, and yet also mutually redundant, in host defense. In combination, the contribution of these two enzymes appears to be greater than previously appreciated. The remainder of this review focuses on a relatively new field, the basis of microbial resistance to RNI. Experimental tuberculosis provides an important example of an extended, dynamic balance between host and pathogen in which RNI play a major role. In diseases such as tuberculosis, a molecular understanding of host–pathogen interactions requires characterization of the defenses used by microbes against RNI, analogous to our understanding of defenses against reactive oxygen intermediates. Genetic and biochemical approaches have identified candidates for RNI-resistance genes in Mycobacterium tuberculosis and other pathogens.
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In the citing paper
“In addition, NO causes the formation of reactive nitrogen species (such as peroxynitrite) which can damage mitochondrial function and which have been shown to have strong antifungal activity (26).”
From Inhibition of Classical and Alternative Modes of Respiration in Candida albicans Leads to Cell Wall Remodeling and Increased Macrophage Recognition (2019) · cites this paper as [26]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“iNOS catalyzed high output formation of the labile radical NO by macrophages (Nathan and Shiloh, 2000; Bogdan, 2001) which exerts direct anti-microbial effector functions.”
From Iron at the interface of immunity and infection (2014) · cites this paper as Nathan and Shiloh, 2000
In the citing paper
“Using arginine and oxygen, the homodimeric NOS2 generates NO and citrulline, as one subunit transfers electrons between NADPH, FAD, flavin mononucleotide to the heme iron of the second subunit (56, 57).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [56]
In the citing paper
“NOX2 consists of five catalytic subunits, which assemble after phagocytosis thereby forming an active enzymatic complex producing superoxide anions and hydrogen peroxide along with the formation of hydroxyl radicals, the latter pathway being catalyzed by iron via the Fenton reaction (56, 59–61).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [56]
In the citing paper
“Both NOX2/gp91 phox and iNOS/ NOS2 are prototypical hemoproteins that use Fe-heme to catalyze the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), respectively [76].”
From The Iron age of host–microbe interactions (2015) · cites this paper as [76]
In the citing paper
“Moreover, extracellular hemoglobin may also exert protective effects based on NO and ONNO À detoxification [76,80,197].”
From The Iron age of host–microbe interactions (2015) · cites this paper as [76]
In the citing paper
“For example, generation of nitric oxide (NO•) by the inducible nitric oxide synthase (iNOS/NOS2) is a well established host defense mechanism that confers resistance to Salmonella, Leishmania or Mycobacteria (62).”
From Innate Nutritional Immunity (2018) · cites this paper as [62]
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Citations
Cites
Nitric oxide as a secretory product of mammalian cells
Nathan, C. (1992) · The FASEB Journal · doi:10.1096/fasebj.6.12.1381691 · Cited by 4,350
Self-citationNITRIC OXIDE AND MACROPHAGE FUNCTION
MacMicking, J. D., Xie, Q. W., & Nathan, C. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.323 · Cited by 4,245
Self-citationPeroxynitrite oxidation of sulfhydryls.
Radí, R., Beckman, J. S., Bush, K., & Freeman, B. Α. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)64313-7 · Cited by 2,492
An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection.
Flynn, J. L., Chan, J., Triebold, K. J., Dalton, D. K., Stewart, T. A., & Bloom, B. R. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.178.6.2249 · Cited by 2,468
Multiple defects of immune cell function in mice with disrupted interferon-gamma genes.
Dalton, D., Pitts-Meek, S., Keshav, S., Figari, I., Bradley, A., & Stewart, T. (1993) · Science · doi:10.1126/science.8456300 · Cited by 2,015
Nitric oxide functions as a signal in plant disease resistance
Delledonne, M., Xia, Y., Dixon, R. A., & Lamb, C. J. (1998) · Nature · doi:10.1038/29087 · Cited by 1,859
Flynn, J. L., Goldstein, M. M., Chan, J., Triebold, K. J., Pfeffer, K., Lowenstein, C. J., Schrelber, R., Mak, T. W., & Bloom, B. R. (1995) · Immunity · doi:10.1016/1074-7613(95)90001-2 · Cited by 1,678
Immune Response in Mice that Lack the Interferon-γ Receptor
Huang, S., Hendriks, W. J. A. J., Althage, A., Hemmi, S., Bluethmann, H., Kamijo, R., Vilček, J., Zinkernagel, R. M., & Aguet, M. (1993) · Science · doi:10.1126/science.8456301 · Cited by 1,551
Defense gene induction in tobacco by nitric oxide, cyclic GMP, and cyclic ADP-ribose
Durner, J., Wendehenne, D., & Klessig, D. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.17.10328 · Cited by 1,320
DNA Deaminating Ability and Genotoxicity of Nitric Oxide and its Progenitors
Wink, D. A., Kasprzak, K. S., Maragos, C. M., Elespuru, R. K., Misra, M., Dunams, T. M., Cebula, T. A., Koch, W. H., Andrews, A. W., Allen, J. S., et al. (1991) · Science · doi:10.1126/science.1948068 · Cited by 1,243
Research works printed but not linked: 6
- S J Klebanoff Inflammation, eds J I Gallin, R Snyderman, D T Fearon, B F Haynes, C Nathan (Lippincott, Philadelphia), pp. 721–768 (1999).
- P Elsbach, J Weiss, O Levy Inflammation, eds J I Gallin, R Snyderman, D T Fearon, B F Haynes, C Nathan (Lippincott, Philadelphia), pp. 801–818 (1999).
- M A DeGroote, F C Fang Nitric Oxide and Infection, ed F C Fang (Kluwer/Plenum, New York), pp. 231–264 (1999).
- J Chan, J Flynn Nitric Oxide and Infection, ed F C Fang (Kluwer/Plenum, New York), pp. 281–310 (1999).
- B Gaston, J S Stamler Nitric Oxide and Infection, ed F C Fang (Kluwer/Plenum, New York), pp. 37–55 (1999).
- Bryk R. Griffin P. & Nathan C. (2000) Nature (London) in press.
Cited by
Sorted by citations
Nitric oxide and the immune response
Bogdan, C. (2001) · Nature Immunology · doi:10.1038/ni1001-907 · Cited by 3,447
Myeloperoxidase: friend and foe
Klebanoff, S. J. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.1204697 · Cited by 2,282
Oxidative Stress, Prooxidants, and Antioxidants: The Interplay
Rahal, A., Kumar, A., Singh, V., Yadav, B., Tiwari, R., Chakraborty, S., & Dhama, K. (2014) · BioMed Research International · doi:10.1155/2014/761264 · Cited by 1,806
Antimicrobial reactive oxygen and nitrogen species: concepts and controversies
Fang, F. C. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro1004 · Cited by 1,676
Graves, D. B. (2012) · Journal of Physics D Applied Physics · doi:10.1088/0022-3727/45/26/263001 · Cited by 1,534
Metadata
- Authors
- Nathan, C., & Shiloh, M. U.
- Affiliations
- Cornell University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-08
- Volume
- 97
- Issue
- 16
- Pages
- 8841-8848
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC34021
- OpenAlex
- W2113120391
- Cited by
- 1,469
- References
- 105
- Citations by year
- 2026: 26 · 2025: 29 · 2024: 42 · 2023: 32 · 2022: 49 · 2021: 42 · 2020: 59 · 2019: 51 · 2018: 56 · 2017: 62 · 2016: 66 · 2015: 64 · 2014: 72 · 2013: 70 · 2012: 81
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- reactive oxygen species, reactive nitrogen intermediates, host-pathogen interaction, inducible nitric oxide synthase, NADPH oxidase, inducible nitric oxide, Mycobacterium tuberculosis, tuberculosis, knockout mice, innate immunity
- MeSH terms
- Animals, Humans, Mammals, Mycobacterium tuberculosis, Nitrogen, Reactive Oxygen Species, Nitric Oxide Synthase, NADPH Oxidases, Mice
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