好中球の殺菌ペプチドｄｅｆｅｎｓｉｎとｃａｔｈｅｌｉｃｉｄｉｎの協同作用

Abstract

Activated neutrophils extracellularly release antibacterial defensins and cathelicidins from the granules. 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) . In the absence of NaCl, human defensin (HNP-1) and guinea pig defensins (GNCPs) exhibited the antibacterial activities against Escherichia coli and Staphylococcus aureus in a dose-dependent manner (0.1-10μg/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 NaCI. 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. 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. Together these observations likely 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 potentiating the membrane permeabilization of target cells.