cytochalasin-b and Pneumonia

Acute 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.

Topics: Actin Cytoskeleton; Actins; Acute Lung Injury; Animals; Bronchoalveolar Lavage Fluid; CD11b Antigen; Cell Adhesion; Cell Movement; Cells, Cultured; Coculture Techniques; Cytochalasin B; Cytokines; Endothelial Cells; Inflammation Mediators; Lipopolysaccharides; Lung; Male; Monocytes; Neutrophil Infiltration; Neutrophils; Pneumonia; Protein Transport; Rats; Rats, Sprague-Dawley; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha