Role of the actin cytoskeleton during respiratory burst in chemoattractant-stimulated neutrophils |
| |
Authors: | Bengtsson Torbjörn Orselius Kristina Wetterö Jonas |
| |
Institution: | 1. Cardiovascular Inflammation Research Centre, Division of Pharmacology, Department of Medicine and Care, Linköping University, SE-581 85 Linköping, Sweden;2. Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Linköping University, SE-581 85 Linköping, Sweden |
| |
Abstract: | The aim of this study was to clarify the role of the actin cytoskeleton during chemotactic peptide fMet-Leu-Phe (fMLF)-stimulated respiratory burst in human neutrophil granulocytes. Reactive oxygen species (ROS) was measured as luminol-amplified chemiluminescence (CL) and F-actin content as bodipy phallacidin fluorescence in neutrophils treated with latrunculin B or jasplakinolide, an inhibitor and activator of actin polymerization, respectively. Latrunculin B markedly decreased, whereas jasplakinolide increased, the F-actin content in neutrophils, unstimulated or stimulated with fMLF. Latrunculin B enhanced the fMLF-triggered ROS-production more than tenfold. Jasplakinolide initially inhibited the fMLF-induced CL-response, however, caused a potent second sustained phase (>400% of control). Both actin drugs triggered a substantial CL-response when added 5-25 min after fMLF. This was also valid for chemotactic doses of fMLF, where latrunculin B and jasplakinolide amplified the ROS-production 5-10 times. By using specific signal transduction inhibitors, we found that the NADPH oxidase activation triggered by destabilization of the actin cytoskeleton occurs downstream of phospholipase C and protein kinase C but is mediated by Rho GTPases and tyrosine phosphorylation. In conclusion, rearrangements of the actin cytoskeleton are a prerequisite in connecting ligand/receptor activation, generation of second messengers and assembly of the NADPH oxidase in neutrophil granulocytes. |
| |
Keywords: | fMet‐Leu‐Phe Neutrophil Actin cytoskeleton Latrunculin Jasplakinolide NADPH oxidase |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|