Analysis of Leukocyte Funcitions in Vitro Elicited by Mannoprotein-β-glucan Complex of Candida albicans, an Inducer of Murine Coronary Arteritis

Abstract

Candida albicans is a medically important fungus, which induces a disseminated candidasis and candidemia in immunocompromised host, and releases polysaccharide fraction into the patient's blood. We had recently found that C. albicans released water-soluble polysaccharide fraction (CAWS) into the synthetic medium and demonstrated that CAWS was mainly composed of a complex of mannan and β-glucan. In murine system, CAWS showed lethality resembled to the anaphylactic shock by i.v., and induced coronary arteritis resembled to KD by i.p.. In this study, we examined the biological activity of CAWS in in vitro cell culture and the results were summarized as follows: i) CAWS inhibited proliferation of splenocytes induced by a B cell mitogen, lipopolysaccharide (LPS) and a T cell mitogen, Concanavalin A dose dependently. ii) Viability of these splenocytes monitored by propidium iodide staining was significantly reduced, iii) Addition of CAWS to the in vitro culture of cell lines, mastocytoma P-815, monophage RAW264.7 and fibroblast L-929 significantly reduced growth rate of these cells dose dependently, iv) LPS mediated cytokine synthesis of RAW264.7 was significantly inhibited by CAWS. v) CAWS induced platelet aggregation by human platelet rich plasma, and vi) CAWS inhibited the production of thrombomodulin from human umbilical endothelial cells and the activity was synergistic with TNF. From the observations, CAWS strongly inhibited cellular functions of leukocytes in vitro and the property would partly be mediated by direct cytotoxic property of CAWS. Enhanced production of injured cells in vascular endothelium would be related to the local inflammatory response in the coronary artery.

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