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

Abstract

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 b b-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-g g and IL-6 by splenocytes at lower dose (ca. 10 m mg/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-a a. 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.

Chemistry and Biology of Angiitis Inducer, Candida albicans Water‐Soluble Mannoprotein‐β‐Glucan Complex (CAWS)

“…We first screened strains of mice for sensitivity to lethal toxicity (16,17). Examination of various strains revealed marked differences in sensitivity among the strains, with C3H exhibiting markedly high sensitivity and DBA/2 exhibiting markedly low sensitivity, and fatality could not be confirmed over the entire range of concentrations used.…”

“…Therefore, the in vitro activity of CAWS was screened using several evaluation systems (17). As a result, it was found that at low concentrations of CAWS, a weak action that promotes the production of cytokines such as IL-6 and IFN-γ was observed in mouse spleen cells.…”

IL-10 Is a Negative Regulatory Factor of CAWS-Vasculitis in CBA/J Mice as Assessed by Comparison with Bruton’s Tyrosine Kinase-Deficient CBA/N Mice

“…administration (12,13). As a positive control, a closed colony of ICR mice was used, in which ϳ100% acute lethal activity is observed.…”

Involvement of Platelet Activating Factor, Histamine and Serotonin in Acute Lethal Shock Induced by Candida albicans Water-Soluble Extracellular Polysaccharide Fraction (CAWS) in Mice

“…CAWS was found to be composed of a mannoprotein-b-glucan complex, to be able to activate limulus G factor, 6) to demonstrate an activating effect on vascular endothelial cells, platelets, and lymphocytes, and to demonstrate vasculitis-inducing activity when administered to mice. [7][8][9][10][11] Moreover, CAWS caused an acute lethal reaction when administered intravenously to mice. The vasculitis was strongly related to the structure of the mannan moiety, and the activity was significantly reduced in the presence of a beta-1,2-linked mannosyl segment which was synthesized under specific conditions.…”