Cited by 457Nitric Oxide and Endothelin EffectsImmune cells in cancerNeutrophil, Myeloperoxidase and Oxidative Mechanisms

The DOI matches its Crossref record; 34 of the 35 references it cites were found in a registry or an index.

Activated murine macrophages secrete a metabolite of arginine with the bioactivity of endothelium-derived relaxing factor and the chemical reactivity of nitric oxide

Open access

Stuehr, D J, Gross, S S, Sakuma, I, Levi, R, Nathan, C F·1989·The Journal of experimental medicine

DOI 10.1084/jem.169.3.1011PMC PMC2189276

Open this paper in CoChat — free account Open PDF

Abstract

L-arginine-dependent synthesis of nitrite (NO2-) and nitrate (NO3-) by macrophages correlates with and is required for their execution of nonspecific cytotoxicity toward some tumor cells and microbes. However, the bioactive L-arginine metabolites responsible for cytotoxicity are unknown. Mammalian endothelial cells have recently been shown to release nitric oxide (NO.); we therefore determined if this reactive metabolite was synthesized by activated murine macrophages. Macrophage-derived NO. was detected by two independent methods: a bioassay for NO.-mediated relaxation of preconstricted rings of rabbit aorta; and a spectroscopic measurement of the reaction of NO. with clostridial ferredoxin, an Fe-S protein. After activation with IFN-gamma and LPS, macrophages continuously secreted a substance that relaxed rabbit aortic rings denuded of endothelium. Production of the vasorelaxant was enhanced by 0.5 mM L-arginine and inhibited reversibly by NG-methylated L-arginine analogs that block macrophage NO2-/NO3- synthesis. The vasorelaxant was scavenged by ferrous myoglobin, was labile, and was neither NO2- nor a cyclooxygenase metabolite. Activated M phi also secreted a substance that bleached Fd, a reaction carried out by NO. and NO2, but not NO2-. Macrophage bleaching of Fd correlated directly with time, cell number, and concomitant NO2-/NO3- production, required L-arginine, and was independent of reactive oxygen intermediates. Thus, activated murine M phi release NO. and/or a closely related, highly reactive nitrogen oxide such as NO2, during their conversion of L-arginine to NO2-/NO3-. NO. and NO2 may mediate L-arginine-dependent pathologic effects of M phi, as well as physiologic effects not previously considered for this widely distributed cell type.

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.

Integrity signals

Registry

Crossref · 10.1084/jem.169.3.1011

Cites

34 of 34 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.

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?

Self-check

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

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

Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Palmer, R. M. J., Ferrige, A. G., & Moncada, S. (1987) · Nature · doi:10.1038/327524a0 · Cited by 10,704
Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide.
Ignarro, L. J., Buga, G. M., Wood, K. S., Byrns, R. E., & Chaudhuri, G. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.24.9265 · Cited by 5,074
Vascular endothelial cells synthesize nitric oxide from L-arginine
Palmer, R. M. J., Ashton, D., & Moncada, S. (1988) · Nature · doi:10.1038/333664a0 · Cited by 4,786
Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production.
Ding, A. H., Nathan, C., & Stuehr, D. J. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.141.7.2407 · Cited by 2,840
Self-citation
Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite
Hibbs, J. B., Taintor, R. R., & Vavrin, Z. (1987) · Science · doi:10.1126/science.2432665 · Cited by 1,527
L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation
Palmer, R. M. J., Rees, D. D., Ashton, D. S., & Moncada, S. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(88)81362-7 · Cited by 1,348
Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta.
Martin, W., Villani, G. M., Jothianandan, D., & Furchgott, R. F. (1985) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)20898-9 · Cited by 1,259
Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide.
Stuehr, D. J., & Marletta, M. A. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.22.7738 · Cited by 1,126
Self-citation
L-arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells.
Hibbs, J. B., Vavrin, Z., & Taintor, R. R. (1987) · The Journal of Immunology · doi:10.4049/jimmunol.138.2.550 · Cited by 938
The Role of Endothelium in the Responses of Vascular Smooth Muscle to Drugs
Furchgott, R. F. (1984) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.24.040184.001135 · Cited by 937

Flagged first, then by citations

Show all 35 references

1 of the 35 references couldn’t be matched to a known paper.

Sorted by citations

Nitric oxide as a secretory product of mammalian cells
Nathan, C. (1992) · The FASEB Journal · doi:10.1096/fasebj.6.12.1381691 · Cited by 4,350
Self-citation
Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells
Stuehr, D. J., & Nathan, C. F. (1989) · The Journal of Experimental Medicine · doi:10.1084/jem.169.5.1543 · Cited by 1,744
Self-citation
Role of nitric oxide synthesis in macrophage antimicrobial activity
Nathan, C. F., & Hibbs, J. B. (1991) · Current Opinion in Immunology · doi:10.1016/0952-7915(91)90079-g · Cited by 1,523
Self-citation
Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide: Implications for neurodegenerative diseases
Cleeter, M. W. J., Cooper, J. M., Darley-Usmar, V. M., Moncada, S., & Schapira, A. H. V. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00424-2 · Cited by 1,241
N OVEL N EURAL M ODULATORS
Boehning, D. F., & Snyder, S. H. (2003) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.26.041002.131047 · Cited by 1,235
Biosynthesis of nitric oxide from l-arginine
Moncada, S., Palmer, R. M. J., & Higgs, E. A. (1989) · Biochemical Pharmacology · doi:10.1016/0006-2952(89)90403-6 · Cited by 1,222
Peroxynitrite formation from macrophage-derived nitric oxide
Ischiropoulos, H., Zhu, L., & Beckman, J. S. (1992) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(92)90433-w · Cited by 1,099
Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells.
Radomski, M. W., Palmer, R. M. J., & Moncada, S. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.24.10043 · Cited by 1,097
Gases as biological messengers: nitric oxide and carbon monoxide in the brain
Dawson, T., & Snyder, S. (1994) · The Journal of Neuroscience · doi:10.1523/jneurosci.14-09-05147.1994 · Cited by 1,043
Mammalian nitric oxide synthases
Stuehr, D. J. (1999) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(99)00016-x · Cited by 996
Self-citation
Inflammation, immunoregulation, and inducible nitric oxide synthase
Nussler, A. K., & Billiar, T. R. (1993) · Journal of Leukocyte Biology · doi:10.1002/jlb.54.2.171 · Cited by 859
Oxidation of nitric oxide in aqueous solution to nitrite but not nitrate: comparison with enzymatically formed nitric oxide from L-arginine
Ignarro, L. J., Fukuto, J. M., Griscavage, J. M., Rogers, N. E., & Byrns, R. E. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.8103 · Cited by 856
Induction of nitric oxide synthase in asthma
Hamid, Q. A., Springall, D., Polak, J. M., Riveros‐Moreno, V., Chanez, P., Bousquet, J., Godard, P., Holgate, S., Howarth, P. H., & Redington, A. E. (1993) · The Lancet · doi:10.1016/s0140-6736(05)80083-2 · Cited by 836
A novel neuronal messenger molecule in brain: The free radical, nitric oxide
Dawson, T. M., Dawson, V. L., & Snyder, S. H. (1992) · Annals of Neurology · doi:10.1002/ana.410320302 · Cited by 828
Molecular Biology of Mammalian Plasma Membrane Amino Acid Transporters
Palacı́n, M., Estévez, R., Bertran, J., & Zorzano, A. (1998) · Physiological Reviews · doi:10.1152/physrev.1998.78.4.969 · Cited by 821
Endogenous nitric oxide: physiology, pathology and clinical relevance
Moncada, S., & Higgs, E. A. (1991) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1991.tb01383.x · Cited by 760
NITRIC OXIDE SYNTHASE: Role in the Genesis of Vascular Disease
Cooke, J. P., & Dzau, V. J. (1997) · Annual Review of Medicine · doi:10.1146/annurev.med.48.1.489 · Cited by 706
The 1991 Ulf von Euler Lecture:The l ‐arginine: nitric oxide pathway
Moncada, S. (1992) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1992.tb09359.x · Cited by 645
Nitrogen oxide levels in patients after trauma and during sepsis
OCHOA, J. B., UDEKWU, A. O., BILLIAR, T. R., CURRAN, R. D., CERRA, F. B., SIMMONS, R. L., & PEITZMAN, A. B. (1991) · Annals of Surgery · doi:10.1097/00000658-199111000-00013 · Cited by 599
New insights into the regulation of inducible nitric oxide synthesis
Morris, S. M., & Billiar, T. R. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.266.6.e829 · Cited by 570
The physiological role of nitric oxide
Butler, A. R., & Williams, D. L. H. (1993) · Chemical Society Reviews · doi:10.1039/cs9932200233 · Cited by 555
Heme Oxygenase-1
Morse, D., & Choi, A. M. K. (2002) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.27.1.4862 · Cited by 535
Signal transduction mechanisms involving nitric oxide
Ignarro, L. J. (1991) · Biochemical Pharmacology · doi:10.1016/0006-2952(91)90618-f · Cited by 524
EPR demonstration of iron-nitrosyl complex formation by cytotoxic activated macrophages
Lancaster, J. R., & Hibbs, J. B. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.3.1223 · Cited by 507
Mammalian Nitric Oxide Synthases
Stuehr, D. J., & Griffith, O. W. (1992) · Advances in enzymology and related areas of molecular biology/Advances in enzymology and related subjects · doi:10.1002/9780470123119.ch8 · Cited by 507
Self-citation
Nitric oxide. A novel signal transduction mechanism for transcellular communication.
Ignarro, L. J. (1990) · Hypertension · doi:10.1161/01.hyp.16.5.477 · Cited by 498
Signaling by Gasotransmitters
Mustafa, A. K., Gadalla, M. M., & Snyder, S. H. (2009) · Science Signaling · doi:10.1126/scisignal.268re2 · Cited by 503
Role of nitric oxide in gastrointestinal and hepatic function and disease
Stark, M. E., & Szurszewski, J. H. (1992) · Gastroenterology · doi:10.1016/0016-5085(92)91454-c · Cited by 481
Nitric oxide in septic shock
Titheradge, M. A. (1999) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(99)00031-6 · Cited by 457
Glucocorticoids inhibit the induction of nitric oxide synthase in macrophages
Rosa, M. D., Radomski, M. W., Carnuccio, R., & Moncada, S. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)91583-e · Cited by 454
Bactericidal activity of peroxynitrite
Zhu, L., Gunn, C., & Beckman, J. S. (1992) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(92)90434-x · Cited by 438
Untitled work
(1991) · doi:10.1172/jci115266 · Cited by 429
Inhibition of tumor cell ribonucleotide reductase by macrophage-derived nitric oxide.
Kwon, N. S., Stuehr, D. J., & Nathan, C. F. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.174.4.761 · Cited by 425
Self-citation
Hepatocytes produce nitrogen oxides from L-arginine in response to inflammatory products of Kupffer cells.
CURRAN, R. D., Billiar, T. R., Stuehr, D. J., Hofmann, K., & Simmons, R. L. (1989) · The Journal of Experimental Medicine · doi:10.1084/jem.170.5.1769 · Cited by 399
Self-citation
Potential genotoxicity of chronically elevated nitric oxide: A review
Liu, R. H., & Hotchkiss, J. H. (1995) · Mutation Research/Reviews in Genetic Toxicology · doi:10.1016/0165-1110(95)90004-7 · Cited by 381
Purification of a soluble isoform of guanylyl cyclase-activating-factor synthase.
Schmidt, H. H. H. W., Pollock, J. S., Nakane, M., Gorsky, L. D., Förstermann, U., & Murad, F. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.2.365 · Cited by 381
Inhibition of insulin secretion by interleukin‐1β and tumour necrosis factor‐α via an L‐arginine‐dependent nitric oxide generating mechanism
Southern, C., Schulster, D., & Green, I. C. (1990) · FEBS Letters · doi:10.1016/0014-5793(90)80502-a · Cited by 362
Why nitric oxide?
Traylor, T. G., & Sharma, V. S. (1992) · Biochemistry · doi:10.1021/bi00126a001 · Cited by 354
Vascular hyporeactivity to vasoconstrictor agents and hemodynamic decompensation in hemorrhagic shock is mediated by nitric oxide.
Thiemermann, C., Szabó, C., Mitchell, J. A., & Vane, J. R. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.1.267 · Cited by 352
Metabolic fate of L-arginine in relation to microbiostatic capability of murine macrophages.
Granger, D. L., Hibbs, J. B., Perfect, J. R., & Durack, D. T. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114422 · Cited by 347
International Union of Pharmacology Nomenclature in Nitric Oxide Research.
Moncada, S., Higgs, A., & Furchgott, R. F. (1997) · PubMed · Cited by 344
Modulation of Nitrogen Oxide Synthesis In Vivo: NG-Monomethyl-L-Arginine Inhibits Endotoxin-Induced Nitrate/Nitrate Biosynthesis While Promoting Hepatic Damage
Billiar, T. R., Curran, R. D., Harbrecht, B. G., Stuehr, D. J., Demetris, A. J., & Simmons, R. L. (1990) · Journal of Leukocyte Biology · doi:10.1002/jlb.48.6.565 · Cited by 335
Self-citation
Immunology of Leishmaniasis
Liew, F. Y., & O’Donnell, C. A. (1993) · Advances in Parasitology/Advances in parasitology · doi:10.1016/s0065-308x(08)60208-0 · Cited by 334
Dexras1
Fang, M., Jaffrey, S. R., Sawa, A., Ye, K., Luo, X., & Snyder, S. H. (2000) · Neuron · doi:10.1016/s0896-6273(00)00095-7 · Cited by 316
Nitric oxide reacts with intracellular glutathione and activates the hexose monophosphate shunt in human neutrophils: evidence for S-nitrosoglutathione as a bioactive intermediary.
Clancy, R. M., Levartovsky, D., Leszczynska-Piziak, J., Yegudin, J., & Abramson, S. B. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.9.3680 · Cited by 308
NO, nitrosonium ions, nitroxide ions, nitrosothiols and iron-nitrosyls in biology: a chemist's perspective
Butler, A. R., Flitney, F. W., & Williams, D. L. H. (1995) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)88968-3 · Cited by 302
The induction of nitric oxide synthase and intestinal vascular permeability by endotoxin in the rat
Boughton-Smith, N. K., Evans, S. M., László, F. A., Whittle, B. J. R., & Moncada, S. (1993) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1993.tb13940.x · Cited by 290
Alterations of ribonucleotide reductase activity following induction of the nitrite-generating pathway in adenocarcinoma cells.
Lepoivre, M., Chénais, B., Yapo, A., Lemaire, G., Thelander, L., & Tenu, J. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)77279-7 · Cited by 285
The Biologically Relevant Coordination Chemistry of Iron and Nitric Oxide: Electronic Structure and Reactivity
Lehnert, N., Kim, E., Dong, H. T., Harland, J. B., Hunt, A. P., Manickas, E. C., Oakley, K. M., Pham, J., Reed, G. C., & Alfaro, V. S. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00253 · Cited by 283
Generation of EPR-detectable nitrosyl-iron complexes in tumor target cells cocultured with activated macrophages
Drapier, J., Pellat‐Deceunynck, C., & Henry, Y. A. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)99204-5 · Cited by 279
Reaction of No With O2−. Implications for the Action of Endothelium-Derived Relaxing Factor (EDRF)
Sarán, M., Michel, C., Bors, W., & Czapski, G. (1990) · Free Radical Research Communications · doi:10.3109/10715769009149890 · Cited by 269
Multiple Cytokines Are Required to Induce Hepatocyte Nitric Oxide Production and Inhibit Total Protein Synthesis
CURRAN, R. D., Billiar, T. R., Stuehr, D. J., Ochoa, J. B., Harbrecht, B. G., FLINT, S. G., & Simmons, R. L. (1990) · Annals of Surgery · doi:10.1097/00000658-199010000-00009 · Cited by 269
Self-citation
Macrophage and endothelial cell nitric oxide synthesis: Cell-type selective inhibition by NG-aminoarginine, NG-nitroarginine and NG-methylarginine
Gross, S. S., Stuehr, D. J., Aisaka, K., JAFFE, E. A., Levi, R., & Griffith, O. W. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)91245-n · Cited by 269
Self-citation
Cytokine-Induced Synthesis of Nitrogen Oxides in Macrophages: A Protective Host Response to Leishmania and Other Intracellular Pathogens
Green, S. J., Nacy, C. A., & Meltzer, M. S. (1991) · Journal of Leukocyte Biology · doi:10.1002/jlb.50.1.93 · Cited by 266
Novel Neurotransmitters and Their Neuropsychiatric Relevance
Snyder, S. H., & Ferris, C. D. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.11.1738 · Cited by 263
Methylene blue administration in septic shock
Preiser, J., Lejeune, P., Roman, A., Carlier, E., Backer, D. D., Leeman, M., Kahn, R. J., & Vincent, J. (1995) · Critical Care Medicine · doi:10.1097/00003246-199502000-00010 · Cited by 262
Personalized disease-specific protein corona influences the therapeutic impact of graphene oxide
Hajipour, M. J., Raheb, J., Akhavan, O., Arjmand, S., Mashinchian, O., Rahman, M., Abdolahad, M., Serpooshan, V., Laurent, S., & Mahmoudi, M. (2015) · Nanoscale · doi:10.1039/c5nr00520e · Cited by 260
Activated macrophages kill pancreatic syngeneic islet cells via arginine-dependent nitric oxide generation
Kröncke, K., Kolb-Bachofen, V., Berschick, B., Burkart, V., & Kolb, H. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(91)91630-u · Cited by 255
Identification of N‐iminoethyl‐ l ‐ornithine as an irreversible inhibitor of nitric oxide synthase in phagocytic cells
McCall, T., Feelisch, M., Palmer, R. M. J., & Moncada, S. (1991) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1991.tb12159.x · Cited by 252
Endogenous nitric oxide inhibits the synthesis of cyclooxygenase products and interleukin-6 by rat Kupffer cells
Stadler, J., Harbrecht, B. G., Silvio, M. D., CURRAN, R. D., Jordan, M. L., Simmons, R. L., & Billiar, T. R. (1993) · Journal of Leukocyte Biology · doi:10.1002/jlb.53.2.165 · Cited by 247
Nitric oxide and carbon monoxide: parallel roles as neural messengers
Snyder, S. H., Jaffrey, S. R., & Zakhary, R. (1998) · Brain Research Reviews · doi:10.1016/s0165-0173(97)00032-5 · Cited by 238
Nitric oxide from L-arginine stimulates the soluble guanylate cyclase in adrenal glands
Palacios‐Callender, M., Knowles, R. G., Palmer, R. M. J., & Moncada, S. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(89)80037-3 · Cited by 237
Haem‐Dependent Activation of Guanylate Cyclase and Cyclic GMP Formation by Endogenous Nitric Oxide: A Unique Transduction Mechanism for Transcellular Signaling
Ignarro, L. J. (1990) · Pharmacology & Toxicology · doi:10.1111/j.1600-0773.1990.tb00772.x · Cited by 229
Nitric oxide and nitric oxide‐generating compounds inhibit hepatocyte protein synthesis
CURRAN, R. D., Ferrari, F. K., Kispert, P. H., Stadler, J., Stuehr, D. J., Simmons, R. L., & Billiar, T. R. (1991) · The FASEB Journal · doi:10.1096/fasebj.5.7.1707021 · Cited by 224
Self-citation
Waging War against UropathogenicEscherichia coli: Winning Back the Urinary Tract
Sivick, K. E., & Mobley, H. L. T. (2009) · Infection and Immunity · doi:10.1128/iai.01000-09 · Cited by 216
Arginine and Citrulline and the Immune Response in Sepsis
Wijnands, K. A. P., Castermans, T. M. R., Hommen, M., Meesters, D. M., & Poeze, M. (2015) · Nutrients · doi:10.3390/nu7031426 · Cited by 217
Redox reactions related to indoleamine 2,3-dioxygenase and tryptophan metabolism along the kynurenine pathway
Thomas, S. R., & Stocker, R. (1999) · Redox Report · doi:10.1179/135100099101534927 · Cited by 215
Electronic Structure of Heme-Nitrosyls and Its Significance for Nitric Oxide Reactivity, Sensing, Transport, and Toxicity in Biological Systems
Goodrich, L. E., Paulat, F., Praneeth, V. K. K., & Lehnert, N. (2010) · Inorganic Chemistry · doi:10.1021/ic902304a · Cited by 204
Nitric oxide, a biological effector
Henry, Y. A., Ducrocq, C., Drapier, J., Servent, D., Pellat‐Deceunynck, C., & Guissani, A. (1991) · European Biophysics Journal · doi:10.1007/bf00183275 · Cited by 205
The arginine‐nitric oxide pathway: A target for new drugs
Kerwin, J. F., & Heller, M. (1994) · Medicinal Research Reviews · doi:10.1002/med.2610140103 · Cited by 202
The actions of nitric oxide donors in the prevention or induction of injury to the rat gastric mucosa
López-Belmonte, J. L., Whittle, B. J. R., & Moncada, S. (1993) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1993.tb13442.x · Cited by 203
Lipopolysaccharide-induced Expression of Interferon-β Mediates the Timing of Inducible Nitric-oxide Synthase Induction in RAW 264.7 Macrophages
Jacobs, A. T., & Ignarro, L. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106639200 · Cited by 197
nitric oxide synthases
Schmidt, H. H. H. W., Pollock, J. S., Nakane, M., Förstermann, U., & Murad, F. (1992) · Cell Calcium · doi:10.1016/0143-4160(92)90055-w · Cited by 196
Immediate release of a nitric oxide-like factor from bovine aortic endothelial cells by Escherichia coli lipopolysaccharide.
Salvemini, D., Korbut, R., Änggård, E., & Vane, J. R. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.7.2593 · Cited by 188
Nitric Oxide Synthases: Gene Structure and Regulation
Wang, Y., & Marsden, P. A. (1995) · Advances in pharmacology · doi:10.1016/s1054-3589(08)61081-9 · Cited by 187
Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health
Koch, C. D., Gladwin, M. T., Freeman, B. A., Lundberg, J. O., Weitzberg, E., & Morris, A. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.12.015 · Cited by 186
Toxoplasma Effector Recruits the Mi-2/NuRD Complex to Repress STAT1 Transcription and Block IFN-γ-Dependent Gene Expression
Olias, P., Etheridge, R. D., Zhang, Y., Holtzman, M. J., & Sibley, L. D. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.06.006 · Cited by 187
IFN-γ-activated macrophages: Detection by electron paramagnetic resonance of complexes between L-Arginine-derived nitric oxide and non-heme iron proteins
Pellat‐Deceunynck, C., Henry, Y. A., & Drapier, J. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)91919-j · Cited by 185
ESTROGENS AND ATHEROSCLEROSIS
Nathan, L., & Chaudhuri, G. (1997) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.37.1.477 · Cited by 179
FAD and GSH participate in macrophage synthesis of nitric oxide
Stuehr, D. J., Kwon, N. S., & Nathan, C. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)92357-6 · Cited by 181
Self-citation
Vascular smooth muscle-derived relaxing factor (MDRF) and its close similarity to nitric oxide
Wood, K. S., Buga, G. M., Byrns, R. E., & Ignarro, L. J. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)91243-l · Cited by 177
Mutagenicity of nitric oxide and its inhibition by antioxidants
Arroyo, P. L., Hatch‐Pigott, V., Mower, H. F., & Cooney, R. V. (1992) · Mutation Research Letters · doi:10.1016/0165-7992(92)90008-6 · Cited by 175
Role of reactive oxygen species in cell toxicity
Sies, H., & de GROOT, H. (1992) · Toxicology Letters · doi:10.1016/0378-4274(92)90230-h · Cited by 171
The Role of Nitric Oxide in Inflammation
Lyons, C. R. (1995) · Advances in immunology · doi:10.1016/s0065-2776(08)60589-1 · Cited by 169
Transforming growth factor β2 inhibits interleukin 1β- and tumour necrosis factor α-induction of nitric oxide synthase in rat renal mesangial cells
Pfeilschifter, J. M., & Vosbeck, K. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(91)91574-v · Cited by 161
Protein Tyrosine Nitration in Cytokine-activated Murine Macrophages
Pfeiffer, S., Lass, A., Schmidt, K., & Mayer, B. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100585200 · Cited by 160
Enzymatic formation of nitrogen oxides from L-arginine in bovine brain cytosol
Schmidt, H. H. H. W., Wilke, P., Evers, B., & Böhme, E. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)91067-x · Cited by 157
L-arginine-dependent reactive nitrogen intermediates as mediators of tumor cell killing by activated macrophages.
Keller, R., Geiges, M., & Keist, R. (1990) · PubMed · Cited by 156
Nitric oxide synthase in cultured endocardial cells of the pig
Schulz, R., Smith, J. A., LEWIS, M. J., & Moncada, S. (1991) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1991.tb12378.x · Cited by 156
Peroxisome proliferator-activated receptor gamma agonists protect cerebellar granule cells from cytokine-induced apoptotic cell death by inhibition of inducible nitric oxide synthase
Heneka, M. T., L. Feinstein, D., Galea, E., Gleichmann, M., Wüllner, U., & Klockgether, T. (1999) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(99)00192-7 · Cited by 150
Synthesis of nitrogen oxides from L-arginine by macrophage cytosol: Requirement for inducible and constitutive components
Stuehr, D. J., Kwon, N. S., Gross, S. S., Thiel, B., Levi, R., & Nathan, C. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)92615-6 · Cited by 149
Self-citation
Inhibition of nitric oxide generation affects the induction of diabetes by streptozocin in mice
Lukić, M. L., Stošić‐Grujičić, S., Ostojić, N., Chan, W. L., & Liew, F. Y. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(91)90978-g · Cited by 145
Interleukin 1 and tumor necrosis factor stimulate cGMP formation in rat renal mesangial cells
Pfeilschifter, J. M., & Schwarzenbach, H. (1990) · FEBS Letters · doi:10.1016/0014-5793(90)81080-8 · Cited by 140
Immunomodulatory Effects of Alginate Oligosaccharides on Murine Macrophage RAW264.7 Cells and Their Structure–Activity Relationships
Xu, X., Wu, X., Wang, Q., Cai, N., Zhang, H., Jiang, Z., Wan, M., & Oda, T. (2014) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf405633n · Cited by 145
Fucoidan induces nitric oxide production via p38 mitogen-activated protein kinase and NF-κB-dependent signaling pathways through macrophage scavenger receptors
Nakamura, T., Suzuki, H., Wada, Y., Kodama, T., & Doi, T. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.02.146 · Cited by 139
Time‐dependent enhancement or inhibition of endotoxin‐induced vascular injury in rat intestine by nitric oxide synthase inhibitors
László, F. A., Whittle, B. J. R., & Moncada, S. (1994) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1994.tb14887.x · Cited by 138
Modulation of platelet aggregation by an l-arginine-nitric oxide pathway
Radomski, M. W., Palmer, R. M. J., & Moncada, S. (1991) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(91)90510-y · Cited by 136
Expression of the Nitric Oxide Synthase 2 Gene Is Not Essential for Early Control ofMycobacterium tuberculosisin the Murine Lung
Cooper, A. M., Pearl, J. E., Brooks, J. V., Ehlers, S., & Orme, I. M. (2000) · Infection and Immunity · doi:10.1128/iai.68.12.6879-6882.2000 · Cited by 133
Second messenger role for NO widens to nervous and immunesystem
Collier, J., & Vallance, P. J. (1989) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(89)80001-x · Cited by 135
Suppression of lymphocyte proliferation through the nitric oxide synthesizing pathway
Albina, J. E., & Henry, W. L. (1991) · Journal of Surgical Research · doi:10.1016/0022-4804(91)90210-d · Cited by 134

Authors: Stuehr, D. J., Gross, S. S., Sakuma, I., Levi, R., & Nathan, C. F.
Affiliations: Cornell University (US)
ORCID: Stuehr, D J
Gross, S S
Sakuma, I
Levi, R
Nathan, C F
Venue: The Journal of experimental medicine
Publisher: Rockefeller University Press
Published: 1989-03-01
Volume: 169
Issue: 3
Pages: 1011-1020
ISSN: 0022-1007 (ISSN-L)
1540-9538
DOI: 10.1084/jem.169.3.1011
PMC: PMC2189276
OpenAlex: W1975644913
Cited by: 457
References: 35
Citations by year: 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 6 · 2015: 8 · 2014: 9 · 2013: 10 · 2012: 4
FWCI: 30.53
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journal of Experimental Medicine (publishedVersion)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Heart, Lung, and Blood Institute (HL37407, HL-34215)
National Cancer Institute (CA-43610)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords: macrophages, nitric oxide, arginine metabolism, endothelium-derived relaxing factor, nitrite, nitrate, vasorelaxation, myoglobin, interferon-gamma, LPS, macrophage activation, reactive nitrogen species, macrophage cytotoxicity
MeSH terms: Animals, Aorta, Arginine, Biological Assay, Biological Factors, Chemistry, Endothelium, Vascular, Ferredoxins, Macrophage Activation, Macrophages, Mice, Inbred C3H, Muscle Relaxation, Muscle, Smooth, Vascular, Nitrates, Nitric Oxide, Nitrites, Nitrogen Dioxide, Rabbits, Spectrophotometry, Mice, Chemical Phenomena

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

Activated murine macrophages secrete a metabolite of arginine with the bioactivity of endothelium-derived relaxing factor and the chemical reactivity of nitric oxide

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks