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Propofol inhibits endogenous formyl peptide-induced neutrophil activation and alleviates lung injury.
- Source :
-
Free radical biology & medicine [Free Radic Biol Med] 2018 Dec; Vol. 129, pp. 372-382. Date of Electronic Publication: 2018 Oct 10. - Publication Year :
- 2018
-
Abstract
- Critically ill patients have a high risk of sepsis. Various studies have demonstrated that propofol has anti-inflammatory effects that may benefit critically ill patients who require anesthesia. However, the mechanism and therapeutic effect remain incompletely understood. Our previous data suggest that propofol can act as a formyl peptide receptor 1 (FPR1) antagonist. Here, we hypothesize that propofol mitigates sepsis-induced acute lung injury (ALI) by inhibiting mitochondria-derived N-formyl peptide-mediated neutrophil activation. Oxidative stress caused by activated neutrophils is involved in the pathogenesis of ALI. In human neutrophils, propofol competitively reduced the release of superoxide and associated reactive oxygen species induced by fMMYALF, a human mitochondria-derived N-formyl peptide, suggesting that propofol effectively suppresses neutrophilic oxidative stress. In addition, propofol significantly inhibited fMMYALF-induced elastase release, chemotaxis, calcium mobilization, and phosphorylation of protein kinase B and mitogen-activated protein kinases. These results indicate that propofol suppresses neutrophil activation by blocking the interaction between endogenous N-formyl peptide and its receptor, FPR1, thus inhibiting downstream signaling. Furthermore, propofol alleviated alveolar wall disruption, edematous changes, and neutrophil infiltration in lipopolysaccharide-induced ALI in mice. Noticeably, propofol improved the survival of sepsis mice. This study indicates that the anti-neutrophil effects of propofol may benefit critically ill septic patients.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Acute Lung Injury chemically induced
Acute Lung Injury genetics
Acute Lung Injury mortality
Animals
Cell Movement drug effects
Chemotactic Factors pharmacology
Gene Expression Regulation
Humans
L-Lactate Dehydrogenase metabolism
Leukocyte Elastase genetics
Leukocyte Elastase metabolism
Lipopolysaccharides administration & dosage
Lung drug effects
Lung immunology
Lung pathology
Male
Mice
Mice, Inbred BALB C
Mitogen-Activated Protein Kinases genetics
Mitogen-Activated Protein Kinases metabolism
Neutrophils immunology
Neutrophils pathology
Oligopeptides pharmacology
Peroxidase genetics
Peroxidase metabolism
Primary Cell Culture
Proto-Oncogene Proteins c-akt genetics
Proto-Oncogene Proteins c-akt metabolism
Reactive Oxygen Species antagonists & inhibitors
Reactive Oxygen Species metabolism
Receptors, Formyl Peptide genetics
Receptors, Formyl Peptide metabolism
Sepsis chemically induced
Sepsis genetics
Sepsis mortality
Signal Transduction
Survival Analysis
Acute Lung Injury prevention & control
Neutrophil Activation drug effects
Neutrophils drug effects
Propofol pharmacology
Sepsis drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4596
- Volume :
- 129
- Database :
- MEDLINE
- Journal :
- Free radical biology & medicine
- Publication Type :
- Academic Journal
- Accession number :
- 30312762
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2018.09.048