Ventilator-induced lung injury and mechanotransduction why should we care 英文参考文献.docVIP

Available online /content/11/5/168 Commentary Ventilator-induced lung injury and mechanotransduction: why should we care? Mingyao Liu1 1Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada Corresponding author: Mingyao Liu, mingyao.liu@utoronto.ca Published: 26 October 2007 Critical Care 2007, 11:168 (doi:10.1186/cc6131) This article is online at /content/11/5/168 ? 2007 BioMed Central Ltd See related research by Li et al, /content/11/5/R89 Abstract Neutrophil recruitment and activation is an important mechanism for lung tissue injury, which is mediated by a group of small molecules, namely chemokines, especially a subgroup of C-X-C chemokines. Interleukin-8 (IL-8) is the best example, which has been shown to be up-regulated by mechanical forces in human lung cells [5]. Rodents do not have the IL-8 gene, but produce macrophage inflammatory protein-2 (MIP-2) and other C-X-C chemokines. Mechanical stretch induced MIP-2 in rat lung cells [6]. Increased MIP-2 in murine lung was observed after high volume ventilation by Dr Li and co-workers [7]. They further questioned that neutrophil migration is mediated by a signal pathway activated by Akt (also called protein kinase B). They used Akt+/- mice, which have lower expression of Akt-1. They also used a chemical inhibitor to prevent the activation of Akt in mice, prior to their exposure to high volume ventilation and/or hyperoxia. Indeed, they demonstrated less lung damage in these experimental settings. This is very exciting, isn’t it? However, it is worth mentioning that the Akt pathway is also critically important for proliferation, survival and migration of cell types other than neutrophiles [8]. Inhibition of this pathway in sepsis related lung injury is detrimental [9,10]. The clinical application of this strategy needs to be cautious. Me