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Cited by 1,523Nitric Oxide and Endothelin EffectsNeutrophil, Myeloperoxidase and Oxidative MechanismsImmune Response and Inflammation

Role of nitric oxide synthesis in macrophage antimicrobial activity

Nathan, Carl F., Hibbs, John B.·1991·Current Opinion in Immunology
DOI 10.1016/0952-7915(91)90079-g
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Abstract

Research over the past 5 years has demonstrated that immunologic activation of mouse macrophages induces the activity of nitric oxide synthase, which oxidizes a guanidino nitrogen of L-arginine, yielding citrulline and the reactive radical, nitric oxide. A review of the biochemistry and immunologic regulation of this pathway in macrophages provides a backdrop against which to evaluate its effector functions. Reports published in the past 2 years suggest that synthesis of NO mediates much of the antimicrobial activity of mouse macrophages against some fungal, helminthic, protozoal and bacterial pathogens.

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  • Highly reactive intermediates execute their microbicidal activity by oxidative destruction of membrane lipids, DNA, thiol and tyrosine residues, whereas NO can exert toxicity by directly targeting iron sulfur clusters of central metabolic enzymes.

    “Nonetheless, these highly reactive intermediates execute their microbicidal activity by oxidative destruction of membrane lipids, DNA, thiol and tyrosine residues, whereas NO can exert toxicity by directly targeting iron sulfur cluster of central metabolic enzymes (57, 58, 70–72).”

    From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [70]

  • ROS and RNS have high affinity toward Fe2+ in prosthetic heme groups or Fe-sulfur clusters of various proteins, including IRPs, whose stability and activity they modulate.

    “Both ROS and RNS have high affinity toward Fe 2+ in the prosthetic heme groups or Fe-sulfur clusters of a variety of proteins [79,80].These include IRPs, to which NO can bind and modulate their stability as well as activity [81,82], resulting in IRE-mediated regulation of Fe metabolism [58,66,[81][82][83][84][85][86].”

    From The Iron age of host–microbe interactions (2015) · cites this paper as [79]

  • NO is produced by conversion of L-arginine to L-citrulline, an enzymatic process controlled by NO-synthases.

    “Nitric oxide (NO) is produced by conversion of L-arginine to Lcitrulline, an enzymatic process controlled by NO-synthases (NOS)”

    From Iron in immune cell function and host defense (2021) · cites this paper as [55]

  • Part of the effects of NO can be traced to the high affinity of NO for iron, whereby the radical targets iron sulfur clusters of central metabolic enzymes in target organisms.

    “Part of those effects can be traced back to the high affinity of NO for iron whereby the radical targets iron sulfur clusters of central metabolic enzymes in target organisms”

    From Iron in immune cell function and host defense (2021) · cites this paper as [55]

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Authors
Nathan, C. F., & Hibbs, J. B.
Affiliations
Cornell University (US)
ORCID
Nathan, Carl F.
Venue
Current Opinion in Immunology
Publisher
Elsevier BV
Published
1991
Volume
3
Issue
1
Pages
65-70
ISSN
0952-7915 (ISSN-L)
DOI
10.1016/0952-7915(91)90079-g
OpenAlex
W2073132923
Cited by
1,523
References
59
Citations by year
2026: 6 · 2025: 17 · 2024: 19 · 2023: 14 · 2022: 27 · 2021: 27 · 2020: 37 · 2019: 34 · 2018: 18 · 2017: 20 · 2016: 32 · 2015: 42 · 2014: 42 · 2013: 35 · 2012: 22
FWCI
10.28
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Current Opinion in Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
nitric oxide, nitric oxide synthase, macrophages, antimicrobial activity, L-arginine, fungal pathogens, helminths, protozoan parasites, pathogenic bacteria, macrophage effector function
MeSH terms
Amino Acid Oxidoreductases, Animals, Bacteria, Fungi, Immunity, Cellular, Macrophage Activation, Nitric Oxide, Nitric Oxide Synthase, Mice, Rats, Eukaryota

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