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Brief Definitive Report

May Ho^a, Michael J. Hickey^a, Allan G. Murray^b, Graciela Andonegui^a, and Paul Kubes^a

^a Immunology Research Group, University of Calgary, Calgary, Alberta, Canada T2N 4N1
^b Division of Nephrology and Immunology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T2N 4N1
Dept. of Microbiology and Infectious Diseases, Health Sciences Centre, Calgary, Alberta, Canada T2N 4N1.403-270-8520403-220-8516

Plasmodium falciparum–infected erythrocytes roll on and/or adhere to CD36, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and P-selectin under shear conditions in vitro. However, the lack of an adequate animal model has made it difficult to determine whether infected erythrocytes do indeed interact in vivo in microvessels. Therefore, we made use of an established model of human skin grafted onto severe combined immunodeficient (SCID) mice to directly visualize the human microvasculature by epifluorescence intravital microscopy. In all grafts examined, infected erythrocytes were observed to roll and/or adhere in not just postcapillary venules but also in arterioles. In contrast, occlusion of capillaries by infected erythrocytes was noted only in approximately half of the experiments. Administration of an anti-CD36 antibody resulted in a rapid reduction of rolling and adhesion. More importantly, already adherent cells quickly detached. The residual rolling after anti-CD36 treatment was largely inhibited by an anti–ICAM-1 antibody. Anti–ICAM-1 alone reduced the ability of infected erythrocytes to sustain rolling and subsequent adhesion. These findings provide conclusive evidence that infected erythrocytes interact within the human microvasculature in vivo by a multistep adhesive cascade that mimics the process of leukocyte recruitment.

Key Words: cytoadherence • adhesion molecules • erythrocytes • malaria • pathogenesis

M. Ho and M.J. Hickey contributed equally to this work.

M.J. Hickey's present address is Baker Medical Research Institute, P.O. Box 6492, St. Kilda Rd. Central, Melbourne, Victoria 8008, Australia.

© 2000 The Rockefeller University Press

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