Cystic fibrosis lung disease: The role of nitric oxide

This review summarizes current knowledge about the role of nitric oxide (NO ) in cystic fibrosis (CF) lung disease. NO is endogenously produced by a gr oup of enzymes, the NO synthases (NOSs). There are three isoforms of NOS, e ach encoded by different genes: neuronal (nNOS), immune or inducible (iNOS) , and endothelial (eNOS) nitric oxide synthase.(1) They all form NO and L-c itrulline by enzymatic oxidation of L-arginine. This reaction requires a nu mber of cosubstrates, including molecular oxygen and tetrahydrobiopterin. I t 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 bacte rial lipopolysaccharide (LPS) as well as proinflammatory cytokines such as interleukin (IL)-1 gamma, IL-2, interferon (IFN)-gamma, and tumor necrosis factor (TNF). In contrast to nNOS and eNOS, activation of iNOS does not req uire an increase in intracellular Ca2+ concentration. (C) 1999 Wiley-Liss. Inc.