Synergistic actions of antibacterial neutrophil defensins and cathelicidins.
OBJECTIVE
Activated neutrophils extracellularly release antibacterial defensins and cathelicidins from the granules. In this study, to elucidate the interactions between defensins and cathelicidins in the extracellular environment, we evaluated the individual and synergistic actions of defensins and cathelicidins in the presence of physiological concentration of NaCl (150 mM).


METHODS
Antibacterial activities against Escherichia coli and Staphylococcus aureus were assessed using human and guinea pig defensins and cathelicidins. Furthermore, the effect of defensins and cathelicidins on membrane permeabilization was examined using E. coli ML-35p, as a target organism.


RESULTS
In the absence of NaCl, human defensin (HNP-1) and guinea pig defensins (GNCPs) exhibited the antibacterial activities in a dose-dependent manner (0.1-10 microg/ml); however, their activities were completely lost in the presence of 150 mM NaCl. In contrast, the antibacterial activities of human cathelicidin (CAP18/LL-37) and guinea pig cathelicidin (CAP11) were resistant to NaCl. Interestingly, HNP-1 and GNCPs synergized with CAP18/LL-37 and CAP11 to enhance the antibacterial activities against E. coli and S. aureus in the presence of 150 mM NaCl (p<0.05). Similarly, HNP-1 and GNCPs were synergistic with CAP18/LL-37 and CAP11 to potentiate the outer and inner membrane permeabilization of E. coli ML-35p (p<0.05).


CONCLUSIONS
Together these observations indicate that when extracellularly released from neutrophils, defensins cannot function as antibacterial molecules by themselves, but can synergistically work with cathelicidins to exert the antibacterial activity in the extracellular milieu by augmenting the membrane permeabilization of target cells.
Nagaoka
I
I
Department of Biochemistry, Juntendo University, School of Medicine, Tokyo, Japan. nagaokai@med.juntendo.ac.jp
Hirota
S
S
Yomogida
S
S
Ohwada
A
A
Hirata
M
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D054804:Cathelicidins; D002463:Cell Membrane Permeability / Q000187:drug effects; D023082:Defensins; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D023084:alpha-Defensins
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D023082:Defensins; D011506:Proteins; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; D012965:Sodium Chloride