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

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 294; no. 4; pp. L632 - L641
• Main Authors: Tang, Peter S, Mura, Marco, Seth, Rashmi, Liu, Mingyao
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.04.2008
• Subjects: Apoptosis; Caspases - metabolism; Cell Death; Cells; Enzyme Activation; Humans; Lung - enzymology; Lung - pathology; Lungs; Lysosomes - pathology; Multiple Organ Failure - etiology; Multiple Organ Failure - pathology; Permeability; Proteases; Respiratory diseases; Respiratory Distress Syndrome, Adult - enzymology; Respiratory Distress Syndrome, Adult - pathology
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00262.2007

1 Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Research Institute, Toronto; and 2 Institute 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 Address for reprint requests and other correspondence: M. Liu, Univ. of Toronto, Toronto Medical Discovery Tower, TMDT 2-814, 101 College St., Toronto, Ontario, Canada M5G 1L7 (e-mail: mingyao.liu{at}utoronto.ca )