Dermaseptin, a peptide antibiotic, stimulates microbicidal activities of polymorphonuclear leukocytes.
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.
Ammar
B
B
Departement de Pharmacologie, CNRS URA 1534, Hôpital Cochin, Paris, France.
Périanin
A
A
Mor
A
A
Sarfati
G
G
Tissot
M
M
Nicolas
P
P
Giroud
J P
JP
Roch-Arveiller
M
M
D000595:Amino Acid Sequence; D029845:Amphibian Proteins; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D002118:Calcium / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology; D015054:Zymosan / Q000494:pharmacology
D029845:Amphibian Proteins; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D007211:Indoles; D008301:Maleimides; D010446:Peptide Fragments; D010455:Peptides; D017382:Reactive Oxygen Species; C070905:dermaseptin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; D009195:Peroxidase; D011493:Protein Kinase C; D010739:Phospholipase D; C070515:bisindolylmaleimide I; D002794:Choline; D002118:Calcium