Cystic fibrosis lung disease: the role of nitric oxide

Pediatr Pulmonol. 1999 Dec;28(6):442-8. doi: 10.1002/(sici)1099-0496(199912)28:6<442::aid-ppul10>;2-4.


This review summarizes current knowledge about the role of nitric oxide (NO) in cystic fibrosis (CF) lung disease. NO is endogenously produced by a group of enzymes, the NO synthases (NOSs). There are three isoforms of NOS, each encoded by different genes: neuronal (nNOS), immune or inducible (iNOS), and endothelial (eNOS) nitric oxide synthase.(1) They all form NO and L-citrulline by enzymatic oxidation of L-arginine. This reaction requires a number of cosubstrates, including molecular oxygen and tetrahydrobiopterin. It is now known whether all three isoenzymes are constitutively expressed in cells of the respiratory tract and that their gene expression is inducible.(2,3) NO production by iNOS, the "high-output" NOS, is stimulated by bacterial lipopolysaccharide (LPS) as well as proinflammatory cytokines such as interleukin (IL)-1gamma, IL-2, interferon (IFN)-gamma, and tumor necrosis factor (TNF). In contrast to nNOS and eNOS, activation of iNOS does not require an increase in intracellular Ca(2+) concentration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Airway Resistance
  • Bronchoalveolar Lavage Fluid / chemistry*
  • Child
  • Child, Preschool
  • Cystic Fibrosis / diagnosis
  • Cystic Fibrosis / metabolism*
  • Female
  • Humans
  • Lung / metabolism
  • Lung / pathology*
  • Male
  • Nitric Oxide / analysis
  • Nitric Oxide / metabolism*
  • Prognosis
  • Respiratory Function Tests
  • Sensitivity and Specificity


  • Nitric Oxide