Alveolar cell death in hyperoxia-induced lung injury

Ann N Y Acad Sci. 2003 Dec;1010:405-16. doi: 10.1196/annals.1299.074.


Exposure to high oxygen concentration causes direct oxidative cell damage through increased production of reactive oxygen species. In vivo oxygen-induced lung injury is well characterized in rodents and has been used as a valuable model of human respiratory distress syndrome. Hyperoxia-induced lung injury can be considered as a bimodal process resulting (1) from direct oxygen toxicity and (2) from the accumulation of inflammatory mediators within the lungs. Both apoptosis and necrosis have been described in alveolar cells (mainly epithelial and endothelial) during hyperoxia. While the in vitro response to oxygen seems to be cell type-dependent in tissue cultures, it is still unclear which are the death mechanisms and pathways implicated in vivo. Even though it is not yet possible to distinguish unequivocally between apo-ptosis, necrosis, or other intermediate form(s) of cell death, a great variety of strategies has been shown to prevent alveolar damage and to increase animal survival during hyperoxia. In this review, we summarize the different cell death pathways leading to alveolar damage during hyperoxia, with particular attention to the pivotal role of mitochondria. In addition, we discuss the different protective mechanisms potentially interfering with alveolar cell death.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Death / drug effects*
  • Humans
  • Hyperoxia
  • Lung / pathology*
  • Oxidative Stress
  • Oxygen / toxicity*
  • Pulmonary Alveoli / pathology*
  • Reactive Oxygen Species
  • Receptors, Tumor Necrosis Factor / drug effects


  • Reactive Oxygen Species
  • Receptors, Tumor Necrosis Factor
  • Caspases
  • Oxygen