Hyperoxia‐induced Cell Death in the Lung‐the Correlation of Apoptosis, Necrosis, and Inflammation

Abstract

Prolonged exposure to hyperoxia causes tissue damage in many organs and tissues. Since the entire surface area of lung epithelium is directly exposed to O2 and other inhaled agents, hyperoxia leads to the development of both acute and chronic lung injuries. These pathologic changes in the lung can also be seen in acute lung injury (ALI) in response to other agents. Simple strategies to mitigate hyperoxia-induced ALI might not be effective by virtue of merely reducing or augmenting the extent of apoptosis of pulmonary cells. Identification of the specific cell types undergoing apoptosis and further understanding of the precise timing of the onset of apoptosis may be necessary in order to gain a greater understanding of the connection between apoptosis and tolerance to hyperoxia and ALI. Attention should also be focused on other forms of non-apoptotic programmed cell death.

Human 8-oxoguanine DNA glycosylase increases resistance to hyperoxic cytotoxicity in lung epithelial cells and involvement with altered MAPK activity

“…In addition, previous studies already indicate discrepancies whether hyperoxia causes apoptosis or necrosis in vivo and in vitro, even in different species of animals. 10,26,45,56,57 Furthermore, isolation and transfection of AECII cells may contribute to complex factors due to the dedifferentiation of the AECII cells in vitro and the difficulty to transduce foreign genes in these cells. 58 Nevertheless, our experiments derived from A549 cells with the confirmation from AECII cells, for the first time, indicate possible cross-talks between the different two groups of functional proteins.…”

Hyperoxia-induced signal transduction pathways in pulmonary epithelial cells☆

“…Under physiological conditions, proliferation and death of lung epithelial cells are under stringent control. However, the production of excessive ROS during exposure to prolonged hyperoxia can trigger the injury and death of epithelial cells in hyperoxic animal lungs and in cell culture model systems [10,11,[24][25][26][27].…”

The Role of Angiopoietin 2 in Hyperoxia-Inuduced Acute Lung Injury

“…27,39,40 The dose and/or duration of hyperoxia exposure can cause different cell types in the lung to undergo death via distinct or overlapping mechanisms. Recent studies from our laboratory and others have added to this pathogenic paradigm by demonstrating that ROS mediate their effects, in part, by inducing an endothelial and epithelial cell death response with features of apoptosis and necrosis 6,20,21,25,36,41,42 and that a variety of exogenously administered regulators inhibit these toxic events by regulating local cell death responses. 5,6,20 In addition, although structural cell apoptosis (such as that seen in HALI) can stimulate tissue inflammation, 43,44 hyperoxia-induced inflammation cannot be attributed solely to the nearby cell death response.…”

“…25,27,32 These processes have been considered operationally and mechanistically distinct cell-death responses. 33,34 This distinction may not be true.…”