Adherence of Candida to Cultured Vascular Endothelial Cells: Mechanisms of Attachment and Endothelial Cell Penetration

Abstract

To elucidate the pathogenesis of hematogenous Candida infections, we developed an in vitro model of Candida adherence to and penetration of human endothelial cells. We enhanced or inhibited adherence in order to probe mechanisms of attachment. Adherence of Candida albicans showed a linear relation to Candida inoculum (range, 10²–10⁵ cfu, r = .99, P<.01) and exceeded that of less virulent Candida species and that of Saccharomyces cerevisiae (P < .01). Candida immune serum blocked attachment (>95% inhibition; P < .001), however, this activity was abolished by immunoprecipitation of immune serum with C albicans mannan (P <.001) and was unaffected by immunoprecipitation with S. cerevisiae mannan or by adsorption with particulate chitin. Adherence was diminished by exposing C albicans to heat (>99% inhibition; P<.01), UV light (98% inhibition; P < .01), or sodium periodate (>72% inhibition; P < .01). An extract from heat-exposed C albicans blocked adherence (>51% inhibition; P < .001). Transmission electron microscopy demonstrated that viable or killed Candida organisms were attached to endothelial cells, were enveloped by membrane processes from the endothelial cell surface, and were incorporated into the endothelial cells within phagosomes. Cytochalasin B blocked incorporation without blocking surface attachment.