During the past two decades, there has been a considerable increase in disseminated candidiasis, particularly in immunocompromised patients, complicated postoperative patients, and neonates in intensive care settings. These studies are designed to elucidate the process by which hematogenously spread Candida organisms traverse the endothelium as they escape from the vascular compartment to invade parenchymal tissues. An in vitro assay has been developed to quantify the adherence of C. albicans and other non-albicans Candida species to human, bovine, and rabbit vascular endothelium. Rabbit antiserum to killed Candida cells has been found to block adherence to rabbit endothelial cells: this antiserum will be absorbed by affinity chromatography to remove the blocking components for indirect identification of Candida constituents responsible for adherence. Further characterization of Candida adherence constituents will be accomplished by removing cell wall (and possibly cell membrane) fractions, selectively inactivating specific components, and coating carrier cells or particles with the removed and treated fractions to quantify adherence. Our blocking antiserum, subjected to affinity chromatography, will be tested against these extracted cell wall fractions for substantiation and further definition of components of Candida which mediate endothelial adherence. Candida adherence to vascular endothelium occurs in a milieu of circulating cellular and humoral components; a unique environment when compared to adherence on epithelial surfaces. Complex interactions between the organism, endothelial cells, and these blood elements are likely. Further studies will focus on four areas within this context: a) exploration of possible endothelial induced improvement in Candida phagocytosis and killing by circulating PMNs and monocytes, b) development of a method to quantify Candida and/or phagocytic cell induced endothelial damage, c) characterization of leukocyte adherence to, and migration through, endothelium invaded by Candida, d) possible modulation of Candida endothelial adherence by specific leukocytic peptides recently defined in amino acid sequence. The long range goal of these studies is to elucidate the mechanisms of Candida adherence and penetration of vascular endothelium, in vitro, so that methods can be developed to modify the events of tissue invasion in the rabbit model of hematogenous candidiasis and ultimately in patients susceptible to invasive hematogenous Candida infections.
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