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ATTENUATION OF CYTOADHERENCE OF PLASMODIUM FALCIPARUM TO MICROVASCULAR ENDOTHELIUM UNDER FLOW BY HEMODILUTION

The cytoadherence of Plasmodium falciparum–infected erythrocytes (IRBCs) to endothelium is mediated by adhesion molecules within the physical constraints of a viscous fluid containing mostly erythrocytes. The volume fraction of erythrocytes (hematocrit) and their physical properties, such as deformability, are important properties of blood that affect cell recruitment to the vascular wall. In the present study, we examined the effect of hematocrit on IRBC rolling and adhesion on human microvascular endothelial cells in a flow chamber system in vitro. We found hematocrit to be a major determinant of IRBC/endothelial cell interactions. There was a 5-fold and 12-fold increase in IRBC rolling and adhesion, respectively, when hematocrit increased from 10% to 30%, as a result of changes in shear rate. Similar effects were seen in the presence of less deformable erythrocytes, serum proteins, and on endothelium stimulated with tumor necrosis factor-. The results indicate that hemorheologic variations are an important determinant of the degree of cytoadherence.

Received September 13, 2004. Accepted for publication November 29, 2004.

Acknowledgments: We thank Dr. Ayodeji Jeje (Department of Chemical and Petroleum Engineering, Univeristy of Calgary) and Dr. Kamala Patel (Department of Physiology and Biophysics, University of Calgary), for helpful discussions, and Dr. Caroline Lane (Valley View Family Practice Clinic, Calgary, Alberta, Canada) for providing skin specimens.

Financial support: This study was supported by a grant from the Anemia Institute of Research and Education (Ontario, Canada) and the Alberta Heritage Foundation for Medical Research (Alberta, Canada) to May Ho and Bryan Yipp.

Authors’ addresses: Christine Flatt, Sheona Mitchell, Bryan Yipp, and May Ho, Department of Microbiology and Infectious Diseases, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1. Sornchai Looareesuwan, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand.

Reprint requests: May Ho, Department of Microbiology and Infectious Diseases, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1, Telephone: 403-220-8516, Fax: 403-270-8520, E-mail: mho{at}ucalgary.ca.

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