Synergistic actions of antibacterial neutrophil defensins and cathelicidins

Objective: Activated neutrophils extracellularly release antibacterial defe nsins and cathelicidins from the granules. In this study, to elucidate the interactions between defensins and cathelicidins in the extracellular envir onment, we evaluated the individual and synergistic actions of defensins an d cathelicidins in the presence of physiological concentration of NaCl (150 mM). Materials and Methods. Antibacterial activities against Escherichia coli an d Staphylococcus aureus were assessed using human and guinea pig defensins and cathelicidins. Furthermore, the effect of defensins and cathelicidins o n 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 defe nsins (GNCPs) exhibited the antibacterial activities in a dose-dependent ma nner (0.1-10 mu g/ml); however, their activities were completely lost in th e presence of 150 mM NaCl. In contrast, the antibacterial activities of hum an cathelicidin (CAP18/LL-37) and guinea pig cathelicidin (CAP11) were resi stant to NaCl. Interestingly, HNP-1 and GNCPs synergized with CAP18/LL-37 a nd CAP11 to enhance the antibacterial activities against E. coli and S. aur eus in the presence of 150 mM NaCl (p<0.05). Similarly, HNP-1 and GNCPs wer e synergistic with CAP18/LL-37 and CAP11 to potentiate the outer and inner membrane permeabilization off. coli ML-35p (p<0.05). Conclusions: Together these observations indicate that when extracellularly released from neutrop hils, defensins cannot function as antibacterial molecules by themselves, b ut can synergistically work with cathelicidins to exert the antibacterial a ctivity in the extracellular milieu by augmenting the membrane permeabiliza tion of target cells.