HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/L632    most recent 00262.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tang, P. S. Articles by Liu, M. Search for Related Content PubMed PubMed Citation Articles by Tang, P. S. Articles by Liu, M.

INVITED REVIEW

Acute lung injury and cell death: how many ways can cells die?

¹Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Research Institute, Toronto; and ²Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

Submitted 6 July 2007 ; accepted in final form 14 January 2008

Apoptosis has been considered as an underlying mechanism in acute lung injury/acute respiratory distress syndrome and multiorgan dysfunction syndrome. Recently, several alternative pathways for cell death (such as caspase-independent cell death, oncosis, and autophagy) have been discovered. Evidence of these pathways in the pathogenesis of acute lung injury has also come into light. In this article, we briefly introduce cell death pathways and then focus on studies related to lung injury. The different types of cell death that occur and the underlying mechanisms utilized depend on both experimental and clinical conditions. Lipopolysaccharide-induced acute lung injury is associated with apoptosis via Fas/Fas ligand mechanisms. Hyperoxia and ischemia-reperfusion injury generate reactive oxidative species, which induce complex cell death patterns composed of apoptosis, oncosis, and necrosis. Prolonged overexpression of inflammatory mediators results in increased production and activation of proteases, especially cathepsins. Activation and resistance to death of neutrophils also plays an important role in promoting parenchymal cell death. Knowledge of the coexisting multiple cell death pathways and awareness of the pharmacological inhibitors targeting different proteases critical to cell death may lead to the development of novel therapies for acute lung injury.

apoptosis; necrosis; caspase-independent cell death; oncosis; acute respiratory distress syndrome

This article has been cited by other articles:

				A. Le, R. Damico, M. Damarla, A. Boueiz, H. H. Pae, J. Skirball, E. Hasan, X. Peng, A. Chesley, M. T. Crow, et al. Alveolar cell apoptosis is dependent on p38 MAP kinase-mediated activation of xanthine oxidoreductase in ventilator-induced lung injury J Appl Physiol, October 1, 2008; 105(4): 1282 - 1290. [Abstract] [Full Text] [PDF]