IAI FigSearch
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tanida, T.
Right arrow Articles by Osaki, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tanida, T.
Right arrow Articles by Osaki, T.

Infection and Immunity, June 2001, p. 3883-3890, Vol. 69, No. 6
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.6.3883-3890.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Lactoferrin Peptide Increases the Survival of Candida albicans- Inoculated Mice by Upregulating Neutrophil and Macrophage Functions, Especially in Combination with Amphotericin B and Granulocyte-Macrophage Colony-Stimulating Factor

Toyohiro Tanida, Fu Rao, Toshihiro Hamada, Eisaku Ueta, and Tokio Osaki*

Department of Oral Surgery, Kochi Medical School, Kohasu, Nankoku-city, Kochi 783-8505, Japan

Received 20 October 2000/Returned for modification 27 December 2000/Accepted 20 March 2001

To develop a new strategy to control candidiasis, we examined in vivo the anticandidal effects of a synthetic lactoferrin peptide, FKCRRWQWRM (peptide 2) and the peptide that mimics it, FKARRWQWRM (peptide 2'). Although all mice that underwent intraperitoneal injection of 5 × 108 Candida cells with or without peptide 2' died within 8 or 7 days, respectively, the survival times of mice treated with 5 to 100 µg of intravenous peptide 2 per day for 5 days after the candidal inoculation were prolonged between 8.4 ± 2.9 and 22.4 ± 3.6 days, depending on the dose of peptide 2. The prolongation of survival by peptide 2 was also observed in mice that were infected with 1.0 × 109 Candida albicans cells (3.2 ± 1.3 days in control mice versus 8.2 ± 2.4 days in the mice injected with 10 µg of peptide 2 per day). In the high-dose inoculation, a combination of peptide 2 (10 µg/day) with amphotericin B (0.1 µg/day) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (0.1 µg/day) brought prolonged survival. With a combination of these agents, 60% of the mice were alive for more than 22 days. Correspondingly, peptide 2 activated phagocytes inducing inducible NO synthase and the expression of p47phox and p67phox, and peptide 2 increased phagocyte Candida-killing activities up to 1.5-fold of the control levels upregulating the generation of superoxide, lactoferrin, and defensin from neutrophils and macrophages. These findings indicated that the anticandidal effects of peptide 2 depend not only on the direct Candida cell growth-inhibitory activity, but also on the phagocytes' upregulatory activity, and that combinations of peptide 2 with GM-CSF and antifungal drugs will help in the development of new strategies for control of candidiasis.

* Corresponding author. Mailing address: Department of Oral Surgery, Kochi Medical School, Kohasu, Oko-cho, Nankoku-city, Kochi 783-8505, Japan. Phone: 088-880-2423. Fax: 088-880-2424. E-mail: ozakit{at}kochi-ms.ac.jp.

Infection and Immunity, June 2001, p. 3883-3890, Vol. 69, No. 6
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.6.3883-3890.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2001 by the American Society for Microbiology. All rights reserved.