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Simvastatin Reduces Endotoxin-Induced Acute Lung Injury by Decreasing Neutrophil Recruitment and Radical Formation

Grommes, Jochen; Vijayan, Santosh; Drechsler, Maik; Hartwig, Helene; Mörgelin, Matthias LU ; Dembinski, Rolf; Jacobs, Michael; Koeppel, Thomas Andreas; Binneboesel, Marcel and Weber, Christian, et al. (2012) In PLoS ONE 7(6).
Abstract
Introduction: Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. As simvastatin exerts protective effects in inflammatory diseases we explored its effects on development of ALI and due to the importance of neutrophils in ALI also on neutrophil effector functions. Methods: C57Bl/6 mice were exposed to aerosolized LPS (500 mg/ml) for 30 min. The count of alveolar, interstitial, and intravasal neutrophils were assessed 4 h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and albumin content in the BAL fluid. In vitro, we analyzed the effect of simvastatin on neutrophil adhesion, degranulation, apoptosis, and formation of reactive oxygen species. To monitor... (More)
Introduction: Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. As simvastatin exerts protective effects in inflammatory diseases we explored its effects on development of ALI and due to the importance of neutrophils in ALI also on neutrophil effector functions. Methods: C57Bl/6 mice were exposed to aerosolized LPS (500 mg/ml) for 30 min. The count of alveolar, interstitial, and intravasal neutrophils were assessed 4 h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and albumin content in the BAL fluid. In vitro, we analyzed the effect of simvastatin on neutrophil adhesion, degranulation, apoptosis, and formation of reactive oxygen species. To monitor effects of simvastatin on bacterial clearance we performed phagocytosis and bacterial killing studies in vitro as well as sepsis experiments in mice. Results: Simvastatin treatment before and after onset of ALI reduces neutrophil influx into the lung as well as lung permeability indicating the protective role of simvastatin in ALI. Moreover, simvastatin reduces the formation of ROS species and adhesion of neutrophils without affecting apoptosis, bacterial phagocytosis and bacterial clearance. Conclusion: Simvastatin reduces recruitment and activation of neutrophils hereby protecting from LPS-induced ALI. Our results imply a potential role for statins in the management of ALI. (Less)
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PLoS ONE
volume
7
issue
6
publisher
Public Library of Science
external identifiers
  • wos:000305337600055
  • scopus:84862201630
ISSN
1932-6203
DOI
10.1371/journal.pone.0038917
language
English
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yes
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d29f08e2-e840-477c-8e41-b737cc31cc23 (old id 2891274)
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2012-08-01 08:53:47
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2017-10-22 04:28:26
@article{d29f08e2-e840-477c-8e41-b737cc31cc23,
  abstract     = {Introduction: Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. As simvastatin exerts protective effects in inflammatory diseases we explored its effects on development of ALI and due to the importance of neutrophils in ALI also on neutrophil effector functions. Methods: C57Bl/6 mice were exposed to aerosolized LPS (500 mg/ml) for 30 min. The count of alveolar, interstitial, and intravasal neutrophils were assessed 4 h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and albumin content in the BAL fluid. In vitro, we analyzed the effect of simvastatin on neutrophil adhesion, degranulation, apoptosis, and formation of reactive oxygen species. To monitor effects of simvastatin on bacterial clearance we performed phagocytosis and bacterial killing studies in vitro as well as sepsis experiments in mice. Results: Simvastatin treatment before and after onset of ALI reduces neutrophil influx into the lung as well as lung permeability indicating the protective role of simvastatin in ALI. Moreover, simvastatin reduces the formation of ROS species and adhesion of neutrophils without affecting apoptosis, bacterial phagocytosis and bacterial clearance. Conclusion: Simvastatin reduces recruitment and activation of neutrophils hereby protecting from LPS-induced ALI. Our results imply a potential role for statins in the management of ALI.},
  author       = {Grommes, Jochen and Vijayan, Santosh and Drechsler, Maik and Hartwig, Helene and Mörgelin, Matthias and Dembinski, Rolf and Jacobs, Michael and Koeppel, Thomas Andreas and Binneboesel, Marcel and Weber, Christian and Soehnlein, Oliver},
  issn         = {1932-6203},
  language     = {eng},
  number       = {6},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Simvastatin Reduces Endotoxin-Induced Acute Lung Injury by Decreasing Neutrophil Recruitment and Radical Formation},
  url          = {http://dx.doi.org/10.1371/journal.pone.0038917},
  volume       = {7},
  year         = {2012},
}