Nitrosative capacity of macrophages is dependent on nitric-oxide synthase induction signals

Michael Graham Espey, Katrina M. Miranda, Ryszard M. Pluta, David A. Wink

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


Nitrosative stress can occur when reactive nitric oxide (NO) species compromise the function of biomolecules via formation of NO adducts on critical amine and thiol residues. The capacity of inducible nitric-oxide synthase (iNOS) to generate nitrosative stress was investigated in the murine macrophage line ANA-1. Sequential activation with the cytokines IFN-γ and either tumor necrosis factor-α or interleukin-1β resulted in the induction of iNOS and production of nitrite (20 nM/min) but failed to elicit nitrosation of extracellular 2,3-diaminonapthalene. Stimulation with IFN-γ and bacterial lipopolysaccharide increased the relative level of iNOS protein and nitrite production of ANA-1 cells 2-fold; however, a substantial level of NO in the media was also observed, and nitrosation of 2,3-diaminonapthalene was increased greater than 30-fold. Selective scavenger compounds suggested that the salient nitrosating mechanism was the NO/O2 reaction leading to N2O3 formation. These data mimicked the pattern observed with a 5 μM concentration of the synthetic NO donor (Z)-1-[N-ammoniopropyl)-N-(n-propyl) amino]diazen-1-ium-1,2-diolate (PAPA/NO). The NO profiles derived from iNOS can be distinct and depend on the inductive signal cascades. The diverse consequences of NO production in macrophages may reside in the cellular mechanisms that control the ability of iNOS to form N2O3 and elicit nitrosative stress.

Original languageEnglish (US)
Pages (from-to)11341-11347
Number of pages7
JournalJournal of Biological Chemistry
Issue number15
StatePublished - Apr 14 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Nitrosative capacity of macrophages is dependent on nitric-oxide synthase induction signals'. Together they form a unique fingerprint.

Cite this