Modeling gas phase nitric oxide release in lung epithelial cells

Jingjing Jiang, Steven George

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Nitric oxide (NO) is present in exhaled breath and is generally considered to be a noninvasive marker of airway inflammation, and is thus of particular relevance to monitoring asthma. NO is produced when l-arginine is converted to l-citrulline by NO synthase (NOS); however, l-arginine is also the substrate for arginase and both enzymes are upregulated in asthma. Recent reports have speculated that enhanced expression of one or both enzymes could lead to a limitation in substrate availability, and hence impact downstream targets or markers such as exhaled NO. The non-linear nature and vastly different kinetics of the enzymes make predictions difficult, particularly over the wide range of enzyme activity between baseline and inflammation. In this study, we developed a steady state model of l-arginine transmembrane transport, NO production, diffusion, and gas phase NO release from lung epithelial cells. We validated our model with experimental results of gas phase NO release and intracellular l-arginine concentration in A549 cells, and then performed a sensitivity analysis to determine relative impact of each enzyme on NO production. Our model predicts intracellular l-arginine and gas phase NO release over a wide range of initial extracellular l-arginine concentrations following stimulation with cytomix (10 ng/ml TNF-α, IL-1β, and INF-γ). Relative sensitivity analysis demonstrates that enhanced arginase activity has little impact on l-arginine bioavailability for NOS. In addition, NOS activity is the dominant parameter which impacts gas phase NO release.

Original languageEnglish (US)
Pages (from-to)275-281
Number of pages7
JournalNitric Oxide - Biology and Chemistry
Issue number3
StatePublished - Oct 30 2011


  • Arginase
  • l-Arginine
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cancer Research


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