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Infection and Immunity, May 2001, p. 2815-2820, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.2815-2820.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Inhibition of Hydrophobic Protein-Mediated Candida albicans Attachment to Endothelial Cells during Physiologic Shear Flow

Pati M. Glee,1,* Jim E. Cutler,2 Evelyn E. Benson,1 Robert F. Bargatze,1 and Kevin C. Hazen3

Ligocyte Pharmaceuticals, Inc., Bozeman, Montana 597181; Department of Microbiology, Montana State University, Bozeman, Montana 597172; and Departments of Pathology and Microbiology, University of Virginia Health System, Charlottesville, Virginia 229083

Received 2 October 2000/Returned for modification 30 October 2000/Accepted 25 January 2001

Adhesion interactions during hematogenous dissemination of Candida albicans likely involve a complex array of host and fungal factors. Possible C. albicans factors include changes in cell surface hydrophobicity and exposed antigens that have been shown in static adhesion assays to influence attachment events. We used a novel in vitro shear analysis system to investigate host-pathogen interactions and the role of fungal cell surface hydrophobicity in adhesion events with human endothelial cells under simulated physiologic shear. Endothelial monolayers were grown in capillary tubes and tested with and without interleukin-1beta activation in buffered medium containing human serum. Hydrophobic and hydrophilic stationary-phase C. albicans yeast cells were infused into the system under shear flow and found to adhere with widely varying efficiencies. The average number of adherent foci was determined from multiple fields, sampled via video microscopy, between 8 and 12 min after infusion. Hydrophobic C. albicans cells demonstrated significantly more heterotypic binding events (Candida-endothelial cell) and greater homotypic binding events (Candida-Candida) than hydrophilic yeast cells. Cytokine activation of the endothelium significantly increased binding by hydrophobic C. albicans compared to unactivated host cells. Preincubation of hydrophobic yeast cells with a monoclonal antibody against hydrophobic cell wall proteins significantly blocked adhesion interactions with the endothelial monolayers. Because the antibody also blocks C. albicans binding to laminin and fibronectin, results suggest that vascular adhesion events with endothelial cells and exposed extracellular matrix may be blocked during C. albicans dissemination. Future studies will address the protective efficacy of blocking or redirecting blood-borne fungal cells to favor host defense mechanisms.

* Corresponding author. Mailing address: LigoCyte Pharmaceuticals, Inc., 920 Technology Blvd., Suite C, Bozeman, MT 59718. Phone: (406) 585-2733. Fax: (406) 585-2766. E-mail: pati.glee{at}ligocyte.com.

Infection and Immunity, May 2001, p. 2815-2820, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.2815-2820.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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