DERMASEPTIN, A PEPTIDE ANTIBIOTIC, STIMULATES MICROBICIDAL ACTIVITIESOF POLYMORPHONUCLEAR LEUKOCYTES

Dermaseptin (DRs S1), a 34-amino acid residue cationic antimicrobial p eptide was studied for its effects on the production of reactive oxyge n species (respiratory burst) and exocytosis of polymorphonuclear leuk ocytes (PMN). Treatment of PMN with DRs S1 (10-100 nM) stimulated sign ificant production of reactive oxygen species (approximately a a-fold increase relative to control) and release of myeloperoxidase. In addit ion, low DRs S1 concentrations (1-10 nM) primed the stimulation of res piratory 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-in duced 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 con centration 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 rol e of dermaseptin in modulating host-defense mechanisms. (C) 1998Academ ic Press.