Neutrophil activation and arteritis induced by C. albicans water-soluble mannoprotein-beta-glucan complex (CAWS)

We have established a mouse model which shows the symptoms of coronary arteritis after consecutive injections of CAWS, which is released from Candida albicans. In this study, we examined neutrophil activation in the initial period after CAWS injection intraperitoneally. During 10 min to 16 h after the injection, blood profiles and neutrophil functions were determined. At the same time, levels of inflammatory cytokines and chemokines in plasma were measured. Furthermore, level of ICAM-1 as a marker of lesion in arterial endothelial cells was measured. Counts of the peripheral leukocytes increased immediately after CAWS injection, especially involving neutrophil. In vitro sensitivity of neutrophils to stimuli was enhanced. Moreover, proinflammatory cytokines (IL-1beta, IL-12 and IL-6) increased in plasma initially followed by an increase in IL-10, G-CSF, MIP-2 and soluble ICAM-1. Locally, ICAM-1 message in arterial walls was significantly increased 16 h after CAWS injection. A decrease in C3 levels was observed in plasma, suggesting complement activation and consumption. In summary, neutrophil activation occurred after CAWS injection, followed by complement activation, and production of proinflammatory cytokines chemokines and G-CSF which may be involved in development of coronary arteritis.