On the expression of nitric oxide synthase by human macrophages. Why no NO?
Abstract
The production of nitric oxide (NO) and its role in the anti-tumor and anti-microbial effects of rodent macrophages appears well established. In contrast, the circumstances required for its release from human monocytes/macrophages and its potential role in human pathology remain controversial. Evidence to be discussed suggests that NO is a redundant, autotoxic, immunosuppressive, and inefficient mediator of macrophage function. For these reasons, the expression of nitric oxide synthase as a rapid-response, high-output effector pathway may have been evolved out of the human monocyte/macrophage response repertoire or severely restricted in its expression. Hypothetical roles for a modest and circumscribed production of NO by human macrophages are proposed.
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Robust expression of iNOS is a hallmark of M1 activation in rodent Mp, although iNOS activity in human Mp appears to be much lower or absent entirely.
“In addition to proinflammatory cytokine production, robust expression of iNOS is a hallmark of M1 activation in rodent Mp [14], although iNOS activity in human Mp appears to be much lower or absent entirely (ϳ20 nmol nitrite/10 6 cells/24 h in rodent M1 Mp; often undetectable in human Mp) [66].”
From Macrophage phenotypes during tissue repair (2013) · cites this paper as [66]
Rodent and human macrophages do not exhibit entirely similar responses to in vitro activation.
“Finally and perhaps most importantly, rodent and human Mp do not exhibit entirely similar responses to in vitro activation [9,34,66,80], and it remains to be determined whether there are also species-dependent differences in Mp function during in vivo tissue repair.”
From Macrophage phenotypes during tissue repair (2013) · cites this paper as [66]
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References 57 · Cited by 213
- Authors
- Albina, J. E.
- Affiliations
- Brown University (US)
- Corresponding author
- Albina, Jorge E
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 1995-12-01
- Volume
- 58
- Issue
- 6
- Pages
- 643-649
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2292329478
- Cited by
- 213
- References
- 57
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 5 · 2016: 1 · 2015: 4 · 2014: 9 · 2013: 9 · 2012: 4
- FWCI
- 13.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM042859, GM-42859)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- nitric oxide synthase, nitric oxide, human macrophages, monocytes, immunosuppression, autotoxicity, macrophage function, antitumor immunity
- MeSH terms
- Arginine, Humans, Macrophages, Nitric Oxide, Nitric Oxide Synthase
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