Effect of CAWS, a Mannoprotein-β-glucan Complex of Candida albicans, on Leukocyte, Endothelial Cell, and Platelet Functions in Vitro

Candida albicans is a medically important fungus which induces a disseminated candidasis and candidemia in immunocompromised hosts, and releases a polysaccharide fraction into the blood. We recently found that C. albicans released a water-soluble polysaccharide fraction (CAWS) into synthetic medium...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2003, Vol.26(2), pp.233-240
Main Authors: Kurihara, Kiyoshi, Shingo, Yuko, Miura, Noriko N., Horie, Shuichi, Usui, Yukio, Adachi, Yoshiyuki, Yadomae, Toshiro, Ohno, Naohito
Format: Article
Language:English
Subjects:
Animals
apoptosis
Biological and medical sciences
Blood Platelets - cytology
Blood Platelets - drug effects
Blood Platelets - physiology
Candida albicans
Candida albicans - chemistry
Candida albicans - isolation & purification
Cell Line
cytotoxicity
Endothelium, Vascular - cytology
Endothelium, Vascular - drug effects
Endothelium, Vascular - physiology
Glucans - chemistry
Glucans - isolation & purification
Glucans - pharmacology
Humans
immunosuppression
Leukocytes - cytology
Leukocytes - drug effects
Leukocytes - physiology
Male
mannan
Medical sciences
Membrane Glycoproteins - chemistry
Membrane Glycoproteins - isolation & purification
Membrane Glycoproteins - pharmacology
Mice
Mice, Inbred C3H
Mice, Inbred DBA
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Summary:Candida albicans is a medically important fungus which induces a disseminated candidasis and candidemia in immunocompromised hosts, and releases a polysaccharide fraction into the blood. We recently found that C. albicans released a water-soluble polysaccharide fraction (CAWS) into synthetic medium and demonstrated that CAWS was mainly composed of a complex of mannan and β-glucan. In the murine system, CAWS showed a lethality resembling anaphylactic shock when administered i.v., and induced coronary arteritis similar to Kawasaki Disease (KD) when given i.p. In the present study, we examined the biological activity of CAWS in the cell culture and found the following: i) CAWS slightly induced production of IFN-γ and IL-6 by splenocytes at lower dose (ca. 10 μg/ml), but at a higher dose strongly inhibited the proliferation of splenocytes induced by a B cell mitogen, lipopolysaccharide (LPS) and a T cell mitogen, concanavalin A. ii) The viability of these splenocytes monitored by propidium iodide staining was significantly reduced. iii) The addition of CAWS to a culture of monophage RAW264.7 cells significantly reduced cellular growth rate dose dependently. iv) The LPS-mediated synthesis of cytokines by RAW264.7 cells was significantly inhibited by CAWS. v) CAWS induced an aggregation of platelets in human platelet-rich plasma, and vi) CAWS inhibited the production of thrombomodulin by human umbilical endothelial cells and acted synergistically with TNF-α. Thus, CAWS strongly inhibited the cellular functions of leukocytes in vitro, partly through direct cytotoxicity. The enhanced production in injured cells of the vascular endothelium would be related to the local inflammatory response in the coronary artery.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.26.233