The DOI matches its Crossref record; 244 of the 245 references it cites were found in a registry or an index.
Antimicrobial reactive oxygen and nitrogen species: concepts and controversies
Abstract
Phagocyte-derived reactive oxygen and nitrogen species are of crucial importance for host resistance to microbial pathogens. Decades of research have provided a detailed understanding of the regulation, generation and actions of these molecular mediators, as well as their roles in resisting infection. However, differences of opinion remain with regard to their host specificity, cell biology, sources and interactions with one another or with myeloperoxidase and granule proteases. More than a century after Metchnikoff first described phagocytosis, and more than four decades after the discovery of the burst of oxygen consumption that is associated with microbial killing, the seemingly elementary question of how phagocytes inhibit, kill and degrade microorganisms remains controversial. This review updates the reader on these concepts and the topical questions in the field.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“After crossing the phagosomal membrane, NO and ROI can spontaneously react in the phagosomal lumen to generate nitrogen dioxide (NO2), peroxynitrite (ONOO−), dinitrogen trioxide (N2O3), nitrosothiols, nitroxyl (HNO), and dinitrosyl-iron complexes (58).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [58]
In the citing paper
“In parallel, activated macrophages produce reactive oxygen intermediates (ROI) via activation of NOX2 (58).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [58]
In the citing paper
“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 [58]
Citations
Cites
1 retracted
The large-conductance Ca2+-activated K+ channel is essential for innate immunity
Ahluwalia, J., Tinker, A., Clapp, L. H., Duchen, M. R., Abramov, A. Y., Pope, S. A. S., Nobles, M., & Segal, A. W. (2004) · Nature · doi:10.1038/nature02356 · Cited by 206
RetractedNitric oxide synthases: Roles, tolls, and controls
Nathan, C., & Xie, Q. W. (1994) · Cell · doi:10.1016/0092-8674(94)90266-6 · Cited by 2,920
Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase.
Xie, Q. W., Kashiwabara, Y., & Nathan, C. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37600-7 · Cited by 2,212 · cited 1×
“together with signalling from proinflammatory cytokines (such as IFNs, IL-1β and TNF-α) triggers signalling cascades that lead to iNOS transcription, including the p38 mitogen-activated protein kinase (MAPK), NF-κB and Janus-activated kinase–signal transducer and activator of transcription–interferon regulatory factor…”
BackgroundImlay, J. A. (2003) · Annual Review of Microbiology · doi:10.1146/annurev.micro.57.030502.090938 · Cited by 2,201
DNA damage and oxygen radical toxicity
Imlay, J. A., & Linn, S. (1988) · Science · doi:10.1126/science.3287616 · Cited by 1,974
Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils
Eiserich, J. P., Hristova, M., Cross, C. E., Jones, A. D., Freeman, B. A., Halliwell, B., & van der Vliet, A. (1998) · Nature · doi:10.1038/34923 · Cited by 1,496
Nathan, C., & Shiloh, M. U. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.16.8841 · Cited by 1,469
MacMicking, J. D., Nathan, C., Hom, G. J., Chartrain, N. A., Fletcher, D. S., Trumbauer, M. E., Stevens, K. A., Xie, Q. W., Sokol, K. A., Hutchinson, N. I., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90085-3 · Cited by 1,445
TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection.
Serbina, N., Salazar-Mather, T. P., Biron, C., Kuziel, W., & Pamer, E. (2003) · Immunity · doi:10.1016/s1074-7613(03)00171-7 · Cited by 1,293
Daugherty, A., Dunn, J. L., Rateri, D. L., & Heinecke, J. W. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117342 · Cited by 1,269
Flagged first, then by citations
1 of the 245 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- Gaston, B. & Stamler, J. S. in Nitric Oxide and Infection (ed. Fang, F. C.) 37–55 (Kluwer Academic/Plenum Publishers, New York, 1999).
- De Groote, M. A. & Fang, F. C. in Nitric Oxide and Infection (ed. Fang, F. C.) 231–261 (Kluwer Academic/Plenum Publishers, New York, 1999).
- Fang, F. C. Nitric Oxide and Infection 517 (Kluwer Academic/Plenum Publishers, New York, 1999). A comprehensive examination of the many roles of NO˙ in infection.
Cited by
Sorted by citations
The microbial nitrogen-cycling network
Kuypers, M. M. M., Marchant, H. K., & Kartal, B. (2018) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2018.9 · Cited by 4,563
Novel cell death program leads to neutrophil extracellular traps
Fuchs, T. A., Abed, U., Goosmann, C., Hurwitz, R., Schulze, I., Wahn, V., Weinrauch, Y., Brinkmann, V., & Zychlinsky, A. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200606027 · Cited by 3,197
Reconciling the chemistry and biology of reactive oxygen species
Winterbourn, C. C. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.85 · Cited by 2,504
Reactive Oxygen Species (ROS)-Based Nanomedicine
Yang, B., Chen, Y., & Shi, J. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00626 · Cited by 2,477
Reactive Species and Antioxidants. Redox Biology Is a Fundamental Theme of Aerobic Life
Halliwell, B. B. (2006) · PLANT PHYSIOLOGY · doi:10.1104/pp.106.077073 · Cited by 2,402
Metadata
- Authors
- Fang, F. C.
- Affiliations
- University of Washington (US)
- Corresponding author
- Fang, Ferric C.
- ORCID
- Fang, Ferric C.
- Venue
- Nature Reviews Microbiology
- Published
- 2004-10
- Volume
- 2
- Issue
- 10
- Pages
- 820-832
- ISSN
- 1740-1526 (ISSN-L)
- 1740-1534
- OpenAlex
- W2066515050
- Cited by
- 1,676
- References
- 245
- Citations by year
- 2026: 56 · 2025: 73 · 2024: 81 · 2023: 72 · 2022: 89 · 2021: 129 · 2020: 104 · 2019: 113 · 2018: 83 · 2017: 88 · 2016: 110 · 2015: 70 · 2014: 93 · 2013: 79 · 2012: 90
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fonds De La Recherche Scientifique - FNRS
- 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 (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- reactive oxygen species, reactive nitrogen species, phagocytes, antimicrobial host defense, phagocytosis, myeloperoxidase, microbial killing, host specificity, respiratory burst
- MeSH terms
- Granulomatous Disease, Chronic, Humans, Immunity, Innate, Phagocytes, Polymorphism, Genetic, Cytokines, Reactive Oxygen Species, Nitric Oxide Synthase, Reactive Nitrogen Species, Nitric Oxide Synthase Type II
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
