CoChat
Sign Up
Cited by 1,126Immune Response and InflammationNitric Oxide and Endothelin EffectsNeutrophil, Myeloperoxidase and Oxidative Mechanisms

Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide.

Open access
Stuehr, D J, Marletta, M A·1985·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.82.22.7738PMC PMC391409
Open this paper in CoChat — free account

Abstract

Escherichia coli lipopolysaccharide (LPS)-induced nitrate biosynthesis was studied in LPS-sensitive C3H/He and LPS-resistant C3H/HeJ mice. Intraperitoneal injection of 15 micrograms of LPS led to a temporary 5- to 6-fold increase in blood nitrate concentration in the C3H/He strain. Levels of nitrate excreted in the urine were also increased. In contrast, no increase was observed in the C3H/HeJ strain with LPS injections up to 175 micrograms. Furthermore, thioglycolate-elicited peritoneal macrophages from C3H/He, but not from C3H/HeJ mice, produced nitrite (60%) and nitrate (40%) when cultured with LPS (10 micrograms/ml). T-lymphocyte addition/depletion experiments showed the presence of T cells enhanced this response. However, LPS did not cause nitrite or nitrate production in cultures of spleen lymphocytes from either strain. LPS-induced nitrate synthesis was also observed with nude mice and CBA/N mice, indicating that neither functional T lymphocytes nor LPS-responsive B lymphocytes were required for the response in vivo. This was consistent with the in vitro results showing macrophages alone were competent. Mycobacterium bovis infection of C3H/He and C3H/HeJ mice resulted in a large increase in nitrate production over the course of the infection for both strains, suggesting T-lymphocyte-mediated activation of macrophages as a potent stimulus for nitrate biosynthesis. The synthesis of nitrite is significant in that it can directly participate in the endogenous formation of nitrosamines and may also be involved in some aspect of the chemistry of cytotoxicity.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.82.22.7738

Cites

35 of 35 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

  • LPS administration to mice leads to as much as 1 mM nitrate/nitrite, while human peak levels are only 50-115 μM.

    “While there are similar resting levels of nitrate (25 μM) and nitrite (1 μM) in both species, administration of LPS to mice led to as much as 1 mM nitrate/nitrite while in humans peak levels were only 50-115 μM [34, 39-42]).”

    From Signaling and stress: The redox landscape in NOS2 biology (2015) · cites this paper as [42]

  • Immune activators such as LPS and IL-2 drive increases in plasma nitrate/nitrite in mice and humans.

    “Early studies demonstrated that immune activators such as LPS and IL-2 clearly drive increases in plasma nitrate/nitrite in mice and in humans [34-42].”

    From Signaling and stress: The redox landscape in NOS2 biology (2015) · cites this paper as [42]

  • Resting nitrate and nitrite levels are similar in mice and humans, at 25 μM nitrate and 1 μM nitrite.

    “While there are similar resting levels of nitrate (25 μM) and nitrite (1 μM) in both species, administration of LPS to mice led to as much as 1 mM nitrate/nitrite while in humans peak levels were only 50-115 μM [34, 39-42]).”

    From Signaling and stress: The redox landscape in NOS2 biology (2015) · cites this paper as [42]

  • Activation of murine macrophages with IFNγ and LPS leads to rapid increases in nitrate/nitrite, reaching >10 μM in media within hours of NOS2 induction.

    “Activation with IFNγ and LPS of murine macrophages leads to significant and rapid increases in nitrate/nitrite, reaching >10 μM in media within hours of NOS2 induction [42].”

    From Signaling and stress: The redox landscape in NOS2 biology (2015) · cites this paper as [42]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 11

  1. [2]Green, L. C., Ruiz De Luzuriaga, K., Wagner, D. A., Rand, W., Istfan, N., Young, V. R. & Tannenbaum, S. R. (1981) Proc. Natl. Acad. Sci. USA 78, 7764–7768.
  2. [7]Juhasz, L., Hill, M. J. & Nagy, G. (1978) in Environmental Aspects of N-Nitroso Compounds, eds. Walker, E. A., Castegnaro, M., Griciute, L. & Lyle, R. E. (Int. Agency Res. Cancer, Lyon, France), Publ. 19, pp. 619–623.
  3. [12]Wagner, D. A., Young, V. R. & Tannenbaum, S. R. (1983) Proc. Natl. Acad. Sci. USA 80, 4518–4521.
  4. [16]Senterfitt, V. C. & Shands, J. W. (1978) Proc. Soc. Exp. Biol. Med. 159, 69–74.
  5. [17]Mishell, B. B. & Shiigi, S. M. (1980) Selected Methods in Cellular Immunology (Freeman, San Francisco), pp. 4–6.
  6. [22]Scher, I. (1981) in Immunologic Defects in Laboratory Animals, ed. Gershwin, M. E. (Plenum, New York), Vol. 1, pp. 163-190.
  7. [21]Scher, I., Zaldivar, N. M. & Mosier, D. E. (1977) in Microbiology 1977, ed. Schlesinger, D. (Am. Soc. Microbiol., Washington, DC), pp. 310–313.
  8. [25]Vogel, S. N. & Rosenstreich, D. L. (1981) in Lymphokines, ed. Pick, E. (Academic, New York), Vol. 3, pp. 149–180.
  9. [26]Scibienski, R. J. (1981) in Immunologic Defects in Laboratory Animals, ed. Gershwin, M. E. (Plenum, New York), Vol. 2, pp. 241–258.
  10. [32]Kindred, B. (1981) in Immunologic Defects in Laboratory Animals, ed. Gershwin, M. E. (Plenum, New York), Vol. 1, pp. 215–265.
  11. [44]Gemsa, D. (1981) in Lymphokines, ed. Pick, E. (Academic, New York), Vol. 3, pp. 33–56.

Cited by

Sorted by citations

Related

Authors
Stuehr, D. J., & Marletta, M. A.
Affiliations
Massachusetts Institute of Technology (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1985-11
Volume
82
Issue
22
Pages
7738-7742
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.82.22.7738
PMC
PMC391409
OpenAlex
W1984997174
Cited by
1,126
References
35
Citations by year
2026: 6 · 2025: 4 · 2024: 10 · 2023: 8 · 2022: 13 · 2021: 11 · 2020: 17 · 2019: 14 · 2018: 18 · 2017: 18 · 2016: 7 · 2015: 16 · 2014: 12 · 2013: 13 · 2012: 31
FWCI
3.77
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (CA-26731)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords
nitrite, macrophages, lipopolysaccharide, Escherichia coli, C3H/He mice, C3H/HeJ mice, T cells, peritoneal macrophages, nitrosamines, cytotoxicity
MeSH terms
Animals, BCG Vaccine, Escherichia coli, Lipopolysaccharides, Macrophage Activation, Macrophages, Mice, Inbred BALB C, Mice, Inbred CBA, Mice, Inbred C3H, Nitrates, Nitrites, T-Lymphocytes, Mice

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