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

Journal Article · Fri Nov 01 04:00:00 EST 1985 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.82.22.7738· OSTI ID:6383114

Stuehr, D J; Marletta, M A

Escherichia coli lipopolysaccharide (LPS)-induced nitrate biosynthesis was studied in LPS-sensitive C3H/He and LPS-resistant C3H/HeJ mice. Intraperitoneal injection of 15 ..mu..g 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 ..mu..g. 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 ..mu..g/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.

• Research Organization: Massachusetts Institute of Technology, Cambridge
• OSTI ID: 6383114
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 82:22; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMAL CELLS
ANIMALS
BACTERIA
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BIOSYNTHESIS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOHYDRATES
CONNECTIVE TISSUE CELLS
ESCHERICHIA COLI
INJECTION
INTAKE
INTRAPERITONEAL INJECTION
LEUKOCYTES
LIPIDS
LIPOPOLYSACCHARIDES
LYMPHOCYTES
MACROPHAGES
MAMMALS
MATERIALS
MICE
MICROORGANISMS
MYCOBACTERIUM
NITRATES
NITROGEN COMPOUNDS
NITROSAMINES
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXYGEN COMPOUNDS
PHAGOCYTES
POLYSACCHARIDES
RODENTS
SACCHARIDES
SOMATIC CELLS
SYNTHESIS
TOXICITY
URINE
VERTEBRATES
WASTES