Synergistic actions of antibacterial neutrophil defensins and cathelicidins (original) (raw)

Abstract.

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).¶Materials and 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 μg/ml); however, their activities were completely lost in the presence of 150mM 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.

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Authors and Affiliations

  1. Department of Biochemistry, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo ku, Tokyo 113-8421, Japan, Fax: +81 338 133 157, e-mail: nagaokai@med.juntendo.ac.jp, , , , , , JP
    I. Nagaoka, S. Hirota & S. Yomogida
  2. Department of Respiratory Medicine, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan, , , , , , JP
    A. Ohwada
  3. Department of Bacteriology, Iwate Medical University, School of Medicine, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan, , , , , , JP
    M. Hirata

Authors

  1. I. Nagaoka
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  2. S. Hirota
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  3. S. Yomogida
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  4. A. Ohwada
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  5. M. Hirata
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Received 8 September 1999; returned for revision 8 October 1999; returned for final revision 25 October 1999; accepted by M. Katori 29 October 1999

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Nagaoka, I., Hirota, S., Yomogida, S. et al. Synergistic actions of antibacterial neutrophil defensins and cathelicidins.Inflamm. res. 49, 73–79 (2000). https://doi.org/10.1007/s000110050561

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