Nitric oxide and redox mechanisms in the immune response

Wink, David A; Hines, Harry B; Cheng, Robert Y S; Switzer, Christopher H; Flores-Santana, Wilmarie; Vitek, Michael P; Ridnour, Lisa A; Colton, Carol A

doi:10.1189/jlb.1010550

Cited by 765Neutrophil, Myeloperoxidase and Oxidative MechanismsRedox biology and oxidative stressNitric Oxide and Endothelin Effects

Nitric oxide and redox mechanisms in the immune response

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Wink, David A, Hines, Harry B, Cheng, Robert Y S, Switzer, Christopher H, Flores-Santana, Wilmarie, Vitek, Michael P, Ridnour, Lisa A, Colton, Carol A·2011·Journal of Leukocyte Biology

DOI 10.1189/jlb.1010550PMC PMC3100761

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Abstract

The role of redox molecules, such as NO and ROS, as key mediators of immunity has recently garnered renewed interest and appreciation. To regulate immune responses, these species trigger the eradication of pathogens on the one hand and modulate immunosuppression during tissue-restoration and wound-healing processes on the other. In the acidic environment of the phagosome, a variety of RNS and ROS is produced, thereby providing a cauldron of redox chemistry, which is the first line in fighting infection. Interestingly, fluctuations in the levels of these same reactive intermediates orchestrate other phases of the immune response. NO activates specific signal transduction pathways in tumor cells, endothelial cells, and monocytes in a concentration-dependent manner. As ROS can react directly with NO-forming RNS, NO bioavailability and therefore, NO response(s) are changed. The NO/ROS balance is also important during Th1 to Th2 transition. In this review, we discuss the chemistry of NO and ROS in the context of antipathogen activity and immune regulation and also discuss similarities and differences between murine and human production of these intermediates.

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nNOS and eNOS are constitutively expressed and produce a low level of NO for short periods (seconds to minutes).
“nNOS and eNOS, which are expressed constitutively, produce a low level of NO for short periods (seconds to minutes).447”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [447]
Three types of NOS have been identified: neuronal NOS (nNOS/NOS1), endothelial NOS (eNOS/NOS3), and inducible NOS (iNOS/NOS2).
“At present, three types of NOS have been identified, including neuronal NOS (nNOS, also named as NOS1), endothelial NOS (eNOS, also named as NOS3), and inducible NOS (iNOS, also named as NOS2).447”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [447]
Intracellular communication and immune response are mediated by at least five classes of endogenously generated reactive small molecules.
“Intracellular communication and immune response are mediated by at least five classes of endogenously generated reactive small molecules (Figure 1): nitric oxide (NO) and reactive nitrogen oxide species (RNS), reactive oxygen species (ROS), eicosanoids and reactive lipid species (formed by oxidation of fatty acids), a variety of sulfur-based species such as hydrogen sulfide (H2S), thiols and disul”
From Signaling and stress: The redox landscape in NOS2 biology (2015) · cites this paper as [3]
An additional mechanism for IL-10 production is through NO-dependent increases of COX2.
“An additional mechanism for IL-10 production is through NO-dependent increases of COX2 [3, 57]].”
From Signaling and stress: The redox landscape in NOS2 biology (2015) · cites this paper as [3]
In chronic disease, persistent wound healing processes can lead to fibrosis or tumor growth.
“In chronic disease, involving extended exposure to pathogens or particulates such as plaques in the brain or following a critical mutation, wound healing processes persist and can lead to fibrosis or tumor growth [3].”
From Signaling and stress: The redox landscape in NOS2 biology (2015) · cites this paper as [3]

Redox signaling molecules can act as sensors that steer inflammatory signaling cascades, for example from a Th1 to a Th2 cytokine response.
“These molecules can act as sensors to steer signaling cascades during inflammation, for example from a T helper (Th) 1 to a Th2 cytokine response [3, 87].”
From Signaling and stress: The redox landscape in NOS2 biology (2015) · cites this paper as [3]
In the phagosome, iron deposition facilitates sterilization together with ROS and nitrite.
“In the phagosome, iron deposition facilitates the sterilization process in conjunction with ROS and nitrite [3].”
From Signaling and stress: The redox landscape in NOS2 biology (2015) · cites this paper as [3]
Lysis of Staphylococcus bacteria involves sequential exposure to respiratory burst followed by •NO exposure.
“Lysis of Staphylococcus bacteria involves the sequential exposure to respiratory burst followed by •NO exposure [126].”
From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [126]
•NO and RNS eradicate bacteria by nitrosylation and oxidation of bacterial macromolecules.
“•NO and RNS eradicate bacteria by nitrosylation and oxidation of bacterial macromolecules [126].”
From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [126]
The •NO/ROS balance is important during the transition from Th1 to Th2.
“The •NO/ROS balance is also important during the transition from Th1 to Th2 [125,126].”
From The Role of Reactive Species on Innate Immunity (2022) · cites this paper as [126]
Recognition of bacteria by macrophages leads to ROS production in different cellular compartments, where they fulfill different antibacterial functions.
“Recognition of bacteria by macrophages leads to ROS production in different cellular compartments, where they fulfill different antibacterial functions.”
From Functions of ROS in Macrophages and Antimicrobial Immunity (2021) · cites this paper as [234]

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Role of neuroinflammation in neurodegeneration development
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“At present, three types of NOS have been identified, including neuronal NOS (nNOS, also named as NOS1), endothelial NOS (eNOS, also named as NOS3), and inducible NOS (iNOS, also named as NOS2).(447) nNOS and eNOS, which are expressed constitutively, produce a low level of NO for short periods (seconds to minutes).”
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Free Radicals Mediate Systemic Acquired Resistance
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Mediators of Inflammation
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The Immunomodulation and Anti-Inflammatory Effects of Garlic Organosulfur Compounds in Cancer Chemoprevention
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The Role of Nitric Oxide in Cancer: Master Regulator or NOt?
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Nitric oxide in cancer metastasis
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Current Advances of Nitric Oxide in Cancer and Anticancer Therapeutics
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The mechanism of microglia-mediated immune inflammation in ischemic stroke and the role of natural botanical components in regulating microglia: A review
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Arginine Deprivation and Immune Suppression in a Mouse Model of Alzheimer's Disease
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Antioxidative nanomaterials and biomedical applications
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Differential coral bleaching—Contrasting the activity and response of enzymatic antioxidants in symbiotic partners under thermal stress
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Reactive oxygen species and colorectal cancer
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Leptospirosis Pathophysiology: Into the Storm of Cytokines
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Role of Honey in Advanced Wound Care
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Authors: Wink, D. A., Hines, H. B., Cheng, R. Y. S., Switzer, C. H., Flores-Santana, W., Vitek, M. P., Ridnour, L. A., & Colton, C. A.
Affiliations: National Institutes of Health (US)
United States Army Medical Research Institute of Infectious Diseases (US)
Radiation Biology Branch, National Cancer Institute, National Institutes of Health , Bethesda, Maryland, USA
Duke Medical Center (US)
Corresponding author: Wink, David A
Colton, Carol A
ORCID: Wink, David A
Hines, Harry B
Cheng, Robert Y S
Switzer, Christopher H
Vitek, Michael P
Ridnour, Lisa A
Colton, Carol A
Venue: Journal of Leukocyte Biology
Publisher: Oxford University Press (OUP)
Published: 2011-01-13
Volume: 89
Issue: 6
Pages: 873-891
ISSN: 0741-5400 (ISSN-L)
1938-3673
DOI: 10.1189/jlb.1010550
PMC: PMC3100761
OpenAlex: W2171480404
Cited by: 765
References: 259
Citations by year: 2026: 25 · 2025: 58 · 2024: 46 · 2023: 57 · 2022: 69 · 2021: 74 · 2020: 56 · 2019: 44 · 2018: 40 · 2017: 60 · 2016: 53 · 2015: 57 · 2014: 48 · 2013: 35 · 2012: 27
FWCI: 3.58
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: Journal of Leukocyte Biology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (R01AG031845, R01AG031124)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords: nitric oxide, reactive oxygen species, reactive nitrogen species, redox signaling, immune regulation, phagosome, immunosuppression, wound healing, Th1/Th2 balance, signal transduction, pathogen eradication
MeSH terms: Animals, Humans, Immunity, Cellular, Nitric Oxide, Oxidation-Reduction, Signal Transduction

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Nitric oxide and redox mechanisms in the immune response

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