Nitric oxide: A cytotoxic activated macrophage effector molecule

https://doi.org/10.1016/S0006-291X(88)80015-9Get rights and content

The experiments reported here identify nitric oxide as a molecular effector of activated macrophage induced cytotoxicity. Cytotoxic activated macrophages synthesize nitric oxide from a terminal guanidino nitrogen atom of L-arginine which is converted to L-citrulline without loss of the guanidino carbon atom. In addition, authentic nitric oxide gas causes the same pattern of cytotoxicity in L10 hepatoma cells as is induced by cytotoxic activated macrophages (iron loss as well as inhibition of DNA synthesis, mitochondrial respiration, and aconitase activity). The results suggest that nitric oxide is the precursor of nitrite/nitrate synthesized by cytotoxic activated macrophages and, via formation of iron-nitric oxide complexes and subsequent degradation of iron-sulfur prosthetic groups, an effector molecule.

References (31)

  • HibbsJ.B. et al.

    Biochem and Biophys Res Commun

    (1984)
  • HibbsJ.B. et al.

    Methods in Enzymology

    (1986)
  • GreenL.C. et al.

    Anal Biochem

    (1982)
  • SalernoJ.C. et al.

    Biochem Biophys Res Commun

    (1976)
  • MeyerJ.

    Arch Biohem Biophys

    (1981)
  • PalmerR.M.J. et al.

    Biochem Biophys Res Commun

    (1988)
  • HibbsJ.B. et al.

    J Immunol

    (1987)
  • StuehrD.J. et al.
  • HibbsJ.B. et al.

    Science

    (1987)
  • StuehrD.J. et al.

    Cancer Research

    (1987)
  • DrapierJ.-C. et al.

    J Immunol

    (1988)
  • IyengarR. et al.
  • DrapierJ.-C. et al.

    J Clin Invest

    (1986)
  • WhartonM. et al.

    J Immunol

    (1988)
  • GrangerD.L. et al.

    J Clin Invest

    (1980)
  • Cited by (1941)

    View all citing articles on Scopus
    View full text