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CAWS, a water-soluble extracellular polysaccharide fraction obtained from the culture supernatant of Candida albicans, is one of the fungal pathogen-associated molecular patterns (PAMPs). It has been reported to show potent activity inducing arteritis and coronaritis in mice. Especially, CAWS-induced arteritis has a 100% incidence and severe mortality in the DBA/2 mouse strain. This artificial vasculitis was reported to provide a good murine model of Kawasaki disease and other inflammatory vascular disease. However, severe mortality was observed only in DBA/2 mice, which is a CAWS-sensitive strain. In this study, to clarify the mechanisms of CAWS-induced arteritis and mortality, we investigated microscopic histopathological changes in cardiovascular tissues in DBA/2 mice. Severe inflammatory infiltration was observed from the external elastic lamina in the aorta and proximal coronary arteries within 1 week after CAWS administration. Severe stenosis of the aorta and coronary arteries was observed more than 3 weeks after CAWS administration. Fibrinoid necrosis was observed in these vessel walls. All CAWS-treated mice died between the fifth and twelfth week after administration. Severe inflammatory change with aortic valve transformation suggested that CAWS-treated mice died of valvular endocarditis or cardiac dysfunction. Based on the simple induction method and complete incidence, these data suggest that CAWS-induced arteritis is a good model of not only Kawasaki disease but also other cardiovascular diseases such as valvular endocarditis.

CAWS is a microbial pathogen-associated molecular patterns (PAMPs) produced by Candida albicans. CAWS is a mannoprotein-beta-glucan complex and secreted into the culture supernatant. CAWS has various biological effects, causing acute shock and disrupting vascular permeability. Intraperitoneal administration of CAWS induces coronary arteritis in various strains of inbred mice. The CAWS-induced coronary arteritis is strain-dependent and most severe in DBA/2 mice with a significant number of these animals expiring with cardiomegaly during the observation period. In vivo and in vitro, splenocytes of DBA/2 mice produced various cytokines, such as IL-6, TNF-alpha, and IFN-gamma in response to CAWS. GM-CSF was also produced in response to CAWS. The production of cytokines was significantly enhanced in the presence of recombinant GM-CSF. In contrast, anti-GM-CSF significantly reduced the production of TNF-alpha and IFN-gamma. Augmented production of cytokines in response to CAWS would be a key to the severity of coronary arteritis.