Skip to main content
SpringerLink
Log in

The Role of Macrophage-Derived Nitric Oxide in Tumor Cell Death

  • Chapter
Nitric Oxide in Transplant Rejection and Anti-Tumor Defense

  • 83 Accesses

Abstract

Activated macrophages can distinguish tumor cells from their normal cellular counterparts and have been shown capable of achieving tumor cell toxicity or growth inhibition. Macrophage-derived nitric oxide can induce apoptotic death in NO-sensitive tumor cells. Studies to be presented in this chapter demonstrate that specific tumor cells are resistant to NO-mediated apoptosis, and several mechanisms for this resistant phenotype are explored.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adams DO, Hamilton TA. The cell biology of macrophage activation. Ann Rev Immunol 1984;2:283–318

    Article  CAS  Google Scholar 

  • Adams DO, Johnson WJ, Marino PA. Mechanisms of target recognition and destruction in macrophage-mediated tumor cytotoxicity. Fed Proc 1982;41:2212–2221

    PubMed  CAS  Google Scholar 

  • Adams DO, Nathan CF. Molecular mechanisms in tumor-cell killing by activated macrophages. Immunol Today 1983;4:166–170

    Article  CAS  Google Scholar 

  • Albina JE, Cui S, Mateo RB, Reichner JS. Nitric oxide-mediated apoptosis in murine peritoneal macrophages. J Immunol 1993;150:5080–5085

    PubMed  CAS  Google Scholar 

  • Albina JE, Mastrofrancesco B. Modulation of glucose metabolism in macrophages by products of nitric oxide synthase. Am J Physiol 1993;264:C1594–C1599

    PubMed  CAS  Google Scholar 

  • Albina JE, Mills CD, Henry WL Jr, Caldwell MD. Regulation of macrophage physiology by L-arginine: Role of the oxidative L-arginine deiminase pathway. J Immunol 1989;143:3641–3646

    PubMed  CAS  Google Scholar 

  • Albina JE, Mills CD, Caldwell MD. Alterations in macrophage physiology associated with the metabolism of L-arginine through the oxidative L-arginine deiminase pathway. In: Nitric Oxide From L-Arginine: A Bioregulatory System, Moncada S, Higgs EA. (Eds) Amsterdam, Elsevie

    Google Scholar 

  • Albina JE, Reichner JS. Nitric oxide in inflammation and immunity. New Horizons: The science and practice of acute medicine. 1995;3:46–64

    CAS  Google Scholar 

  • Alexander P, Evans R. Endotoxin and double stranded RNA render macrophages cytotoxic. Nature New Biol 1971;232:76–78

    PubMed  CAS  Google Scholar 

  • Butte TM, Sandstrom PA. Oxidative stress as a mediator of apoptosis. Immunol Today 1994;15:7–10

    Article  Google Scholar 

  • Colin ZA. The activation of mononuclear phagocytes: Fact, fancy and future. J Immunol 1978;121:813–816

    Google Scholar 

  • Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas: with a report of ten original cases. Am J Med Sci 1893;105:487–511

    Article  Google Scholar 

  • Cui S, Reichner JS, Mateo RB, Albina JE. Activated murine macrophages induce apoptosis in tumor cells through nitric oxide-dependent or independent mechanisms. Cancer Res 1994;54:2462–2467

    PubMed  CAS  Google Scholar 

  • Ding AH, Nathan CF, Stuehr DJ. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages: Comparison of activating cytokines and evidence for independent production. J Immunol 1988;141:2407–2412

    PubMed  CAS  Google Scholar 

  • Drapier J-C, Hibbs JB Jr. Differentiation of murine macrophages to express nonspecific cytotoxicity for tumor cells results in L-arginine-dependent inhibition of mitochondrial iron-sulfur enzymes in the macrophage effector cells. J Immunol 1988;140:2829–2838

    PubMed  CAS  Google Scholar 

  • Feelish M. The biochemical pathways of nitric oxide formation from nitrovasodilators: Appropriate choice of exogenous NO donors and aspects of preparation and handling of aqueous NO solutions. J Cardiovasc Pharmacol 1991;17:25–33

    Article  Google Scholar 

  • Granger DL, Lehninger AL. Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells. J Cell Biol 1982;95:527–535

    Article  PubMed  CAS  Google Scholar 

  • Granger DL, Taintor RR, Cook JL, Hibbs JB Jr. Injury of neoplastic cells by murine macrophages leads to inhibition of mitochondrial respiration. J Clin Invest 1980;65:357–370

    Article  PubMed  CAS  Google Scholar 

  • Häussinger D. Hepatocyte heterogeneity in glutamine and ammonia metabolism and the role of an intercellular glutamine cycle during ureogenesis in perfused rat liver. Eur J Biochem 1983; 133:269–275

    Article  PubMed  Google Scholar 

  • Hibbs JB Jr. Activated macrophages as cytotoxic effector cells. II. Requirement for local persistence of inducing antigen. Transplantation 1975; 19:81–87

    Article  PubMed  CAS  Google Scholar 

  • Hibbs JB Jr, Lambert LH Jr, Remington JS. Resistance to murine tumors conferred by chronic infection with intracellular protozoa, Toxoplasma gondii and Besnoitia jellisoni. J Infect Dis 1971; 124:587–592

    Article  PubMed  Google Scholar 

  • Hibbs JB Jr, Lambert LH Jr, Remington JS. Possible role of macrophage mediated nonspecific cytotoxicity in tumour resistance. Nature New Biol 1972;235:48–50

    PubMed  Google Scholar 

  • Hibbs JB Jr, Taintor RR, Vavrin Z. Iron depletion: possible cause of tumor cell cytotoxicity induced by activated macrophages. Biochem Biophys Res Comm 1984;123:716–723

    Article  PubMed  CAS  Google Scholar 

  • Hibbs JB Jr, Taintor RR, Vavrin Z. Macrophage cytotoxicity: Role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science 1987;235:473–476

    Article  PubMed  CAS  Google Scholar 

  • Hibbs JB Jr, Taintor RR, Vavrin Z, Rachlin EM. Nitric oxide: A cytotoxic activated macrophage effector molecule. Biochem Biophys Res Comm 1988;157:87–94

    Article  PubMed  CAS  Google Scholar 

  • Hibbs JB Jr, Taintor RR, Vavrin Z, Granger DL, Drapier J-C, Amber D, Lancaster JR Jr. Synthesis of nitric oxide from a terminal guanidino nitrogen atom of L-arginine: a molecular mechanism regulating cellular proliferation that targets intracellular iron. In: Nitric O

    Google Scholar 

  • Hibbs JB Jr, Vavrin Z, Taintor RR. L-arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells. J Immunol 1987; 138:550–565

    PubMed  CAS  Google Scholar 

  • Hockenbery DM, Oltavi ZN, Yin X-M, Milliman CL, Korsmeyer SJ. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 1993;75:241–251

    Article  PubMed  CAS  Google Scholar 

  • Keller R. Cytostatic elimination of syngeneic rat tumor cells in vitro by nonspecifically activated macrophages. J Exp Med 1973;138:625–644

    Article  PubMed  CAS  Google Scholar 

  • Keller R, Geiges M, Keist R. L-arginine-dependent reactive nitrogen intermediates as mediators of tumor cell killing by activated macrophages. Cancer Res 1990;50:1421–1425

    PubMed  CAS  Google Scholar 

  • Klostergaard J, Leroux ME, Hung M-C. Cellular models of macrophage tumoricidal effector mechanisms in vitro. Characterization of cytolytic responses to tumor necrosis factor and nitric oxide pathways in vitro. J Immunol 1991;147:2802–2808

    PubMed  CAS  Google Scholar 

  • Mateo RB, Reichner J, Mastrofrancesco B, Kraft-Stolar D, Albina JE. Impact of nitric oxide on macrophage glucose metabolism and glyceraldehyde-3-phosphate dehydrogenase activity. Am J Physiol 1995;268:C669–C675

    PubMed  CAS  Google Scholar 

  • Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JS, Tannenbaum SR. DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci USA 1992;89:3030–3034

    Article  PubMed  CAS  Google Scholar 

  • Radi R, Beckman JS, Bush KM, Freeman BA. Peroxynitrite-induced membrane lipid peroxidation: The cytotoxic potential of superoxide and nitric oxide. J Biol Chem 1991;266:4244–4250

    PubMed  CAS  Google Scholar 

  • Sidney MM, Billiar TR. New insights into the regulation of inducible nitric oxide synthesis. Am J Physiol 1994;E829–E839

    Google Scholar 

  • Soo Kwon N, Stuehr DJ, Nathan CF. Inhibtion of tumor cell ribonucleotide reductase by macrophage-derived nitric oxide. J Exp Med 1991;174:761–767

    Article  Google Scholar 

  • Stuehr DJ, Nathan CF. Nitric oxide: A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J Exp Med 1989;169:1543–1555

    Article  PubMed  CAS  Google Scholar 

  • Takema M, Inaba K, Uno K, Kakihara K-I, Tawara K, Muramatsu S. Effect of L-arginine on the retention of macrophage tumoricida1 activity. J Immunol 1991;146:1928–1933

    PubMed  CAS  Google Scholar 

  • Vedia LMY, McDonald B, Reep B, Brune B, Di Silvio M, Billiar TR, Lapetina EG. Nitric oxide-induced S-nitrosylation of giyceraldehyde-3-phosphate dehydrogenase inhibits enzymatic activity and increases endogenous ADP-ribosylation. J Biol Chem 1992;267:24929–24932

    Google Scholar 

  • Yim C-Y, Hibbs JB Jr, McGregor JR, Galinsky RE, Samlowski WE. Use of N-acetyl-cysteine to increase intracellular glutathione during the induction of antitumor responses by IL-2. J Immunol 1994;152:5796–5805

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Rhode Island Hospital, and Brown University School of Medicine, Providence, Rhode Island, 02903, USA

    Jonathan S. Reichner & Jorge E. Albina

Authors
  1. Jonathan S. Reichner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jorge E. Albina
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. The Jagiellonian University, Poland

    Stanislaw Lukiewicz

  2. Johns Hopkins University School of Medicine, USA

    Jay L. Zweier

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Science+Business Media New York

About this chapter

Cite this chapter

Reichner, J.S., Albina, J.E. (1998). The Role of Macrophage-Derived Nitric Oxide in Tumor Cell Death. In: Lukiewicz, S., Zweier, J.L. (eds) Nitric Oxide in Transplant Rejection and Anti-Tumor Defense. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5081-5_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-5081-5_16

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7311-7

  • Online ISBN: 978-1-4615-5081-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation