Phagocyte oxidants and nitric oxide in cystic fibrosis: New therapeutic targets?

Albert Van Der Vliet, Carroll E Cross

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Chronic persistent respiratory tract (RT) infection and overly exuberant activation of host inflammatory-immune processes represent the paramount pathobiologic consequences of cystic fibrosis (CF). The host inflammatory-immune system activation includes the production of reactive oxygen species (ROS) and nitric oxide (NO), which are helpful in RT antimicrobial defenses but under conditions of excess are believed to be harmful to host tissues. However, the genetic defect underlying CF is recognized to uniquely affect inflammatory-immune (oxidative) processes, including alterations in cytokine release, phagocyte activation, antioxidant mechanisms, and NO synthesis and metabolism, and these appear to contribute importantly to the persistent inflammation and infection in patients with CF. The dysregulation of inflammatory-immune responses has also been observed in CF epithelial cells and in some mouse models of CF, and marked advances in our understanding of these processes can be expected from future studies in such model systems. The emerging ideas of how ROS may influence molecular events that control inflammatory protease/antiprotease homeostasis and RT epithelial cell signaling and gene expression, and the role that augmentation of local antioxidant micronutrients (aerosolized and/or systemically administrated) might play in these effects, still remain to be further established and clarified. Further understanding of these processes can be expected to play an important role in future treatment directed toward the devastating effects of CF on the RT of patients with this disorder. (C) 2000 Lippincott Williams and Wilkins, Inc.

Original languageEnglish (US)
Pages (from-to)533-539
Number of pages7
JournalCurrent Opinion in Pulmonary Medicine
Volume6
Issue number6
StatePublished - 2000

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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