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

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

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Stuehr, D J, Marletta, M A·1985·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.82.22.7738PMC PMC391409

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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.

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Authors: Stuehr, D. J., & Marletta, M. A.
Affiliations: Massachusetts Institute of Technology (US)
ORCID: Stuehr, D J
Marletta, M A
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: green
www.ncbi.nlm.nih.gov
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 (medical) › 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

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

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