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Primed neutrophils require phosphatidic acid for maximal receptor-activated elastase release
D Y Tamura1, E E Moore, D A Partrick
1Denver Health Medical Center, University of Colorado Health Sciences Center, Denver, Colorado, 80204, USA.
The Journal of Surgical Research
|August 12, 1998
Summary
Phosphatidic acid (PA) production is essential for neutrophil elastase release in acute respiratory distress syndrome (ARDS). Blocking PA production reduces protease release, indicating PA as a therapeutic target for hyperinflammatory diseases.
Area of Science:
- Immunology
- Cellular Biology
- Biochemistry
Background:
- Neutrophil (PMN) priming for protease release contributes to ARDS/MOF pathogenesis.
- Phospholipase D (PLD) produces phosphatidic acid (PA), crucial for reactive oxygen species but its role in degranulation is unclear.
Purpose of the Study:
- To investigate the role of PLD-produced PA in neutrophil elastase release.
- To test the hypothesis that primed neutrophils require PA for maximal elastase release.
Main Methods:
- Human PMNs were treated with ethanol (PA production antagonist), primed, and activated.
- Exogenous PA was used to mimic or restore elastase release.
- Elastase release was quantified via substrate cleavage.
Main Results:
- Ethanol dose-dependently inhibited elastase release from primed/activated PMNs.
- Exogenous PA restored maximal elastase release, even after ethanol treatment.
Conclusions:
- Neutrophil elastase release is dependent on PA production.
- PA is involved in neutrophil cytotoxicity and represents a potential therapeutic target for ARDS/MOF.