Histopathological Examination and Analysis of Mortality in DBA/2 Mouse Vasculitis Induced with CAWS, a Water-soluble Extracellular Polysaccharide Fraction Obtained from <i>Candida albicans</i>

Abstract

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 artiˆcial vasculitis was reported to provide a good murine model of Kawasaki disease and other in‰ammatory 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 in‰ammatory inˆltration 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 theˆfth and twelfth week after administration. Severe in‰ammatory 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.

β-mannosyl linkages inhibit CAWS arteritis by negatively regulating dectin-2-dependent signaling in spleen and dendritic cells

“…Our research group applied CAWS to this model and demonstrated that arteritis, similar to that by CADS, was induced, and have begun precisely analyzing CAWS-induced vasculitis (CAWS-vasculitis) 3 . The coronary arteritis induced by CAWS was accompanied by hypertrophy of the tunica intima, the rupture of elastic fibers, diffuse invasion by lymphocytes, histiocytes, fibroblasts, smooth muscle cells, and eosinophils of vascular endothelial cells, and lesions surrounding blood vessels 4 . Based on such characteristics, the coronary arteritis induced by CAWS was presumed to be proliferative granulomatous coronary arteritis, which is different from fibrinoid arteritis.…”

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

“…Analysis of serial sections of the aorta stained with H&E suggested that the vasculitis in CBA/N mice was mild compared with that in DBA/2 mice, because aortic stenosis was mild and no reduction in survival rate was observe after CAWS administration (10,14). Previous studies have shown that elastic fiber injury occurs in the aorta close to the beginning of the coronary artery in mice that develop CAWS-vasculitis (10). A similar phenomenon was observed in CBA/N mice as well.…”

“…It was reported that CAWS-vasculitis begins to develop ϳ1 wk after CAWS administration (10). Using ELISA, serum cytokine production was measured in the late phase after CAWS administration (4 mg/0.2 ml PBS) when the vasculitis was thought to have developed (Fig.…”

Candida albicans–associated necrotizing vasculitis producing life-threatening gastrointestinal hemorrhage

“…In a mouse model, intraperitoneal injection of CAWS produces coronary arteritis in 100% of cases with fatal outcome in one particular strain, the DBA/2 mouse [8], whereas 71% C3H/HeN mice were affected, and none of the CBA/JN mice developed arteritis, suggesting genetic susceptibility [9]. This group has demonstrated linkage between susceptibility to arteritis in mice and loci on chromosome 1 that include inflammatory cytokine receptors such as interluekin-1 receptor (IL-1R) and tumor necrosis factor receptor (TNFR).…”