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Dermaseptin, a peptide antibiotic, stimulates microbicidal activities of polymorphonuclear leukocytes
1Departement de Pharmacologie, CNRS URA 1534, Hôpital Cochin, Paris, France.
Abstract:
Dermaseptin (DRs S1), a 34-amino acid residue cationic antimicrobial peptide was studied for its effects on the production of reactive oxygen species (respiratory burst) and exocytosis of polymorphonuclear leukocytes (PMN). Treatment of PMN with DRs S1 (10-100 nM) stimulated significant production of reactive oxygen species (approximately a 2-fold increase relative to control) and release of myeloperoxidase. In addition, low DRs S1 concentrations (1-10 nM) primed the stimulation of respiratory burst induced by zymosan particles. In contrast to the native peptide, a dermaseptin fragment without either the COOH-terminal (DRs 1-10) or NH2 terminal (DRs 16-34) portion was inactive. The DRs S1-induced respiratory burst was inhibited by a selective protein kinase C inhibitor, GF 109203X, and was associated with early signalling events such as a rapid and transient elevation of cytosolic-free calcium concentration and phospholipase D activity. These data provide the first evidence of stimulating and priming properties of a peptide antibiotic on microbicidal activities of neutrophils, suggesting a potential role of dermaseptin in modulating host-defense mechanisms.
Insights
Dermaseptin (DRs S1) stimulates neutrophils to produce reactive oxygen species and prime their respiratory burst. This antimicrobial peptide shows potential in modulating host-defense mechanisms.
Area of Science:
- Immunology
- Biochemistry
- Pharmacology
Background:
- Antimicrobial peptides (AMPs) are crucial in innate immunity.
- Neutrophils play a key role in host defense through microbicidal activities.
- Dermaseptin (DRs S1) is a cationic antimicrobial peptide.
Purpose of the Study:
- To investigate the effects of DRs S1 on polymorphonuclear leukocyte (PMN) functions.
- To explore the mechanisms underlying DRs S1-induced PMN activation.
- To assess the potential of DRs S1 in modulating host-defense.
Main Methods:
- Treatment of PMNs with varying concentrations of DRs S1.
- Measurement of reactive oxygen species (ROS) production and myeloperoxidase release.
- Assessment of calcium signaling and phospholipase D activity.
Main Results:
- DRs S1 (10-100 nM) significantly stimulated ROS production and myeloperoxidase release in PMNs.
- Low DRs S1 concentrations (1-10 nM) primed zymosan-induced respiratory burst.
- DRs S1-induced ROS production was inhibited by a protein kinase C inhibitor and involved calcium and phospholipase D signaling.
Conclusions:
- DRs S1 exhibits both stimulating and priming properties on neutrophil microbicidal activities.
- The peptide's activity is dependent on its structural integrity.
- DRs S1 may play a role in host-defense mechanisms by modulating neutrophil responses.