title: Antimicrobial decapeptide KSL-W enhances neutrophil chemotaxis and function.
abstract: Mammalian cationic antimicrobial peptides have received increased attention over the last decade, due to their prokaryotic selectivity and decreased risk of microbial resistance. In addition, antimicrobial peptides display differential biological effects on mammalian immune cell function, such as migration, adhesion, and modulation of respiratory burst, which make them even more attractive as therapeutic agents. Synthetic combinatorial libraries provide a time-efficient and cost-effective source for these diverse molecules. The novel synthetic antimicrobial peptide, KSLW (KKVVFWVKFK-NH(2)), has been shown to display a broad spectrum of antimicrobial activity against Gram (+) and Gram (-) bacteria, fungi and viruses. In this study, we evaluated the alternative biological activity of the decapeptide on neutrophil migration and function. KSLW was demonstrated to be chemotactic for neutrophils in micromolar amounts, and neutrophil treatment with KSLW, after 1 min, resulted in significant increases in F-actin polymerization. KSLW was shown to inhibit oxygen radical production in PMA- and LPS-stimulated neutrophils. Future studies, to determine if KSLW regulates neutrophil phagocytosis, adhesion, and apoptosis, or examining the effect of KSLW on other mammalian cell types, such as cell populations of healing-impaired wounds, would provide significant insight for the potential therapeutic strategies offered by antimicrobial peptides.
authors.affiliation: US Army Institute of Surgical Research, Fort Sam Houston, TX, United States. richard.williams15@amedd.army.mil
authors.forename: Richard L
authors.initials: RL
authors.lastname: Williams
authors.forename: Herve Y
authors.initials: HY
authors.lastname: Sroussi
authors.forename: Kai
authors.initials: K
authors.lastname: Leung
authors.forename: Phillip T
authors.initials: PT
authors.lastname: Marucha
mesh_terms: D000199:Actins / Q000378:metabolism; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D047630:Depsipeptides / Q000737:chemistry*; D006801:Humans; D009504:Neutrophils / Q000187:drug effects*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D037342:Pertussis Toxin / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000199:Actins; D000890:Anti-Infective Agents; D047630:Depsipeptides; D010455:Peptides; C119235:lysyl-lysyl-valyl-valyl-phenylalanyl-lysyl-valyl-lysyl-phenylalanyl-lysine; D037342:Pertussis Toxin; D013755:Tetradecanoylphorbol Acetate