• Lei Du, Jing Zhou, Jie Zhang, Min Yan, Lina Gong, Xinhao Liu, Mi Chen, Kaiyu Tao, Nanfu Luo, and Jin Liu.
• Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, 37 Wainan Guoxuexiang, Chengdu, Sichuan 610041, China. scudulei@gmail.com
• Am. J. Respir. Cell Mol. Biol. 2012 Nov 1;47(5):597-603.

AbstractAcute lung injury (ALI) induced by systemic inflammatory response syndrome (SIRS) is characterized by deterioration in pulmonary function and leukocyte-associated lung inflammation. Actin fragment (F-actin) reorganization is required for leukocyte activation, adhesion, and transcription of inflammatory factors. We tested the hypothesis that F-actin plays a central role in SIRS-induced ALI. ALI was produced in a rat model with extracorporeal circulation. Cytochalasin B (CB) pretreatment to block F-actin reorganization improved oxygenation and reduced BAL inflammatory factors and pulmonary neutrophil sequestration, but did not reduce the adhesive molecules of blood leukocytes. We challenged blood neutrophils with TNF-α in vitro to explore the underlying mechanisms. Upon activation, neutrophils became polarized and formed a protrusive leading edge, with an aggregation of CD11b molecules. This effect could be blocked by CB, leading to reduced neutrophil adhesion. In addition, after LPS challenge, we observed F-actin reorganization and the up-regulation of inflammatory factors in pulmonary monocytes, which could also be blocked by CB pretreatment. F-actin reorganization initiates lung inflammation via increased blood neutrophil adhesion and migration, and by the production of inflammatory factors by pulmonary monocytes. Thus, blocking F-actin reorganization may potentially prevent and treat SIRS-induced ALI.

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