Cellular mechanisms of nonspecific immunity to intracellular infection: cytokine-induced synthesis of toxic nitrogen oxides from L-arginine by macrophages and hepatocytes

Immunology Letters
S J GreenC A Nacy

Abstract

Nitric oxide (NO) produced by cytokine-treated macrophages and hepatocytes plays a vital role in protective host responses to infectious pathogens. NO inhibits iron-sulfur-dependent enzymes involved in cellular respiration, energy production, and reproduction. Synthesis of L-arginine-derived nitrite (NO2-), the oxidative end product of NO, directly correlates with intracellular killing of Leishmania major, an obligate intracellular protozoan parasite of macrophages: the level of NO2- production is a quantitative index for macrophage activation. The competitive inhibitor of NO synthesis, monomethylarginine (NGMMLA), inhibits both parasite killing and NO2- production. For Leishmania, the parasite itself participates in the regulation of this toxic effector mechanism. This participation is mediated by parasite induction of tumor necrosis factor alpha (TNF alpha), an autocrine factor of macrophages: NO synthesis by interferon-gamma (IFN-gamma)-treated cells can be blocked by monoclonal antibodies to TNF alpha. NO production by IFN gamma-treated hepatocytes is of special interest in malaria infections: sporozoite-infected hepatocytes kill the intracellular malaria parasite after treatment with IFN gamma; this killing is inhibited by...Continue Reading

References

Feb 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J R Lancaster, J B Hibbs
Jan 1, 1990·The Journal of Clinical Investigation·D L GrangerD T Durack
Nov 1, 1989·The Journal of Experimental Medicine·R D CurranR L Simmons
Nov 30, 1988·Biochemical and Biophysical Research Communications·J B HibbsE M Rachlin
Sep 4, 1986·The New England Journal of Medicine·J A AlvarezA Nuñez

❮ Previous
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Citations

Mar 17, 2004·European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery·Bor-Hwang KangHsing-Won Wang
Mar 1, 1995·Veterinary Parasitology·G H Palmer, T F McElwain
Feb 11, 1991·Current Opinion in Immunology·C F Nathan, J B Hibbs
Jan 7, 1999·Clinica Chimica Acta; International Journal of Clinical Chemistry·K Z Kedziora-KornatowskaW Pawlak
Sep 3, 1998·European Journal of Pharmacology·A HrabákB Vray
Jun 14, 2001·International Journal for Parasitology·D Derouich-GuergourH Pelloux
Aug 2, 2001·Toxicon : Official Journal of the International Society on Toxinology·S R ZamunerC F Teixeira
Feb 24, 2001·The Journal of Experimental Medicine·D R RoachW J Britton
Jan 1, 1996·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·S K PuriR K Maheshwari
Sep 6, 2011·European Heart Journal·Ulrich Förstermann, William C Sessa
Oct 1, 1996·Alcoholism, Clinical and Experimental Research·S S GreenbergT D Giles
Dec 3, 1998·Alcoholism, Clinical and Experimental Research·X ZhaoS S Greenberg
Jun 11, 1998·Alcoholism, Clinical and Experimental Research·C A ColtonO N Chernyshev
May 11, 1999·Alcoholism, Clinical and Experimental Research·S S GreenbergJ Ouyang
Jan 1, 1992·The Journal of protozoology·K Fischer-StengerF Marciano-Cabral
Sep 10, 1998·American Journal of Respiratory and Critical Care Medicine·B WeinbergerD L Laskin
Jul 24, 2004·The Journal of Parasitology·Marcelle Carolina ColhoneSelma Giorgio
Dec 7, 2006·American Journal of Pharmaceutical Education·Blase Billack
Dec 19, 1992·Lancet·G SenaldiG E Grau
Apr 5, 2016·Pharmacognosy Reviews·Uorakkottil IlyasPunnooth Poonguzi Naseef
Jan 30, 2013·Brain, Behavior, and Immunity·Jennifer L SzczytkowskiDonald T Lysle
Nov 26, 2015·Acta Tropica·Vívian Tamietti MartinsEduardo Antonio Ferraz Coelho
Oct 13, 2015·Parasite Immunology·Daniela Pagliara LageEduardo Antonio Ferraz Coelho
May 6, 2015·European Journal of Medicinal Chemistry·Aurelia Magdalena Pisoschi, Aneta Pop
Aug 31, 2006·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·John N CurranDavid Bouchier-Hayes
Apr 20, 2010·Parasite Immunology·N M SoaresL Pontes-de-Carvalho
Jul 23, 2014·BioMed Research International·Juliana Reis MachadoDenise Bertulucci Rocha Rodrigues
May 31, 2011·Biochemical and Biophysical Research Communications·Ki Chan KimChan Young Shin

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