EPR demonstration of iron-nitrosyl complex formation by cytotoxic activated macrophages

Journal Article · Thu Feb 01 04:00:00 EST 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.3.1223· OSTI ID:7027397

Lancaster, Jr, J R; Hibbs, Jr, J B ^[1]

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1. Utah State Univ., Logan (USA)

Activated macrophage cytotoxicity is characterized by loss of intracellular iron and inhibition of certain enzymes that have catalytically active nonheme-iron coordinated to sulfur. This phenomenon involves the oxidation of one of the terminal guanidino nitrogen atoms of L-arginine, which results in the production of citrulline and inorganic nitrogen oxides (NO2-, NO3-, and NO). We report here the results of an electron paramagnetic resonance spectroscopic study performed on cytotoxic activated macrophage (CAM) effector cells, which develop the same pattern of metabolic inhibition as their targets. Examination of activated macrophages from mice infected with Mycobacterium bovis (strain bacillus Calmette-Guerin) that were cultured in medium with lipopolysaccharide and L-arginine showed the presence of an axial signal at g = 2.039, which is similar to previously described iron-nitrosyl complexes formed from the destruction of iron-sulfur centers by nitric oxide (NO). Inhibition of the L-arginine-dependent pathway by addition of NG-monomethyl-L-arginine (methyl group on a terminal guanidino nitrogen) inhibits the production of nitrite, nitrate, citrulline, and the g = 2.039 signal. Comparison of the hyperfine structure of the signal from cells treated with L-arginine with terminal guanidino nitrogen atoms of natural abundance N14 atoms or labeled with N15 atoms showed that the nitrosyl group in this paramagnetic species arises from one of these two atoms. These results show that loss of iron-containing enzyme function in CAM is a result of the formation of iron-nitrosyl complexes induced by the synthesis of nitric oxide from the oxidation of a terminal guanidino nitrogen atom of L-arginine.

• OSTI ID: 7027397
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:3; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMAL CELLS
ANIMALS
ARGININE
BACTERIAL DISEASES
BIOSYNTHESIS
CARBOHYDRATES
CARBOXYLIC ACIDS
CELL CULTURES
CHALCOGENIDES
COMPLEXES
CONNECTIVE TISSUE CELLS
DISEASES
ELECTRON SPIN RESONANCE
ELEMENTS
INFECTIOUS DISEASES
IRON
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIPIDS
LIPOPOLYSACCHARIDES
MACROPHAGES
MAGNETIC RESONANCE
MAMMALS
METABOLISM
METALS
MICE
NITRIC OXIDE
NITROGEN 14
NITROGEN 15
NITROGEN COMPOUNDS
NITROGEN ISOTOPES
NITROGEN OXIDES
NONMETALS
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
PHAGOCYTES
POLYSACCHARIDES
RESONANCE
RODENTS
SACCHARIDES
SOMATIC CELLS
STABLE ISOTOPES
SULFUR
SYNTHESIS
TRACER TECHNIQUES
TRANSITION ELEMENTS
TUBERCULOSIS
VERTEBRATES