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Cited by 1,469Neutrophil, Myeloperoxidase and Oxidative MechanismsTuberculosis Research and EpidemiologyRedox biology and oxidative stress

Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens

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Nathan, Carl, Shiloh, Michael U.·2000·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.97.16.8841PMC PMC34021
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Abstract

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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Crossref · 10.1073/pnas.97.16.8841

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  • 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.

    “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 <i>Candida albicans</i> Leads to Cell Wall Remodeling and Increased Macrophage Recognition (2019) · cites this paper as [26]

    The opening passage (labeled Abstract in our copy; page unavailable) says nitric oxide and superoxide form peroxynitrite, a particularly destructive reactive nitrogen intermediate. The host-defense passage reports that NOS2 inhibitors exacerbate infections involving fungi, but the copy does not establish strong antifungal activity specifically for peroxynitrite or describe damage to mitochondrial function. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • iNOS catalyzed high output formation of NO by macrophages exerts direct anti-microbial effector functions.

    “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

  • 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.

    “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]

  • NOX2 consists of five catalytic subunits, which assemble after phagocytosis 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.

    “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]

  • NOX2/gp91phox and iNOS/NOS2 are prototypical hemoproteins that use Fe-heme to catalyze the production of reactive oxygen species and reactive nitrogen species, respectively.

    “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]

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Cites

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1 of the 105 references couldn’t be matched to a known paper.

Research works printed but not linked: 13

  1. [1]Klebanoff S J. In: Inflammation. Gallin J I, Snyderman R, Fearon D T, Haynes B F, Nathan C, editors. Philadelphia: Lippincott; 1999. pp. 721–768. [Google Scholar]
  2. [2]Nathan C. FASEB J. 1992;6:3051–3064. [PubMed] [Google Scholar]
  3. [4]Zingarelli B, O'Connor M, Wong H, Salzman A L, Szabo C. J Immunol. 1996;156:350–358. [PubMed] [Google Scholar]
  4. [11]Shiloh M U, Nathan C. In: Phagocytosis: The Host. Gordon S, editor. Vol. 5. Greenwich, CT: JAI Press; 1999. pp. 407–439. [Google Scholar]
  5. [14]Elsbach P, Weiss J, Levy O. In: Inflammation. Gallin J I, Snyderman R, Fearon D T, Haynes B F, Nathan C, editors. Philadelphia: Lippincott; 1999. pp. 801–818. [Google Scholar]
  6. [23]Gomes M S, Florido M, Pais T F, Appelberg R. J Immunol. 1999;162:6734–6739. [PubMed] [Google Scholar]
  7. [26]DeGroote M A, Fang F C. In: Nitric Oxide and Infection. Fang F C, editor. New York: Kluwer/Plenum; 1999. pp. 231–264. [Google Scholar]
  8. [44]Chan J, Flynn J. In: Nitric Oxide and Infection. Fang F C, editor. New York: Kluwer/Plenum; 1999. pp. 281–310. [Google Scholar]
  9. [54]Jin D-Y, Jeang K-T. In: Antioxidation and Redox Regulation of Genes. Sen C K, Sies H, Baeuerle P A, editors. New York: Academic; 2000. pp. 381–407. [Google Scholar]
  10. [84]Gaston B, Stamler J S. In: Nitric Oxide and Infection. Fang F C, editor. New York: Kluwer/Plenum; 1999. pp. 37–55. [Google Scholar]
  11. [92]Radi R, Beckman J S, Bush K M, Freeman B A. J Biol Chem. 1991;266:4244–4250. [PubMed] [Google Scholar]
  12. [104]Flynn J L, Scanga C A, Tanaka K E, Chan J. J Immunol. 1998;160:1796–1803. [PubMed] [Google Scholar]
  13. [108]Bryk, R., Griffin, P. & Nathan, C. (2000) Nature (London), in press. [DOI] [PubMed]

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Authors
Nathan, C., & Shiloh, M. U.
Affiliations
Cornell University (US)
ORCID
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
DOI
10.1073/pnas.97.16.8841
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
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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