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Characterization of Plasmodium falciparum-Infected
Erythrocyte and P-Selectin Interaction Under Flow Conditions
May Ho,
Tineke Schollaardt,
Xiaofei Niu,
Sornchai Looareesuwan,
Kamala D. Patel, and
Paul Kubes
From the Department of Microbiology and Infectious Diseases,
University of Calgary, Calgary, Alberta, Canada; the
Immunology Research Group, University of Calgary, Calgary,
Alberta, Canada; and the Faculty of Tropical Medicine, Mahidol
University, Bangkok, Thailand.
Plasmodium falciparum-infected erythrocytes
(IRBC) roll on the adhesion molecule P-selectin in vitro
under flow conditions that approximate the shear stress in capillary
and postcapillary venules in which cytoadherence occurs in vivo. The
pathological significance of this adhesive interaction is currently
unknown. In this study, we further investigated the molecular
interactions between IRBC and P-selectin by using a laminar flow system
that allowed for the direct visualization of IRBC-substratum
interactions. The results showed that the IRBC-P-selectin interaction
was Ca2+-dependent and involved the lectin domain of
P-selectin and a sialic acid residue on IRBC. The sialylated P-selectin
ligand was trypsin-sensitive, which suggests that it could be part of the parasite antigen PfEMP1 that interacts with CD36 and intercellular adhesion molecule-1 (ICAM-1), but different from a
trypsin-resistant IRBC ligand that adheres selectively to chondroitin
sulfate A. Studies on the rolling and adhesion of IRBC on activated
platelets that express both CD36 and P-selectin showed that inhibition
of rolling on P-selectin reduced the adhesion of some clinical parasite isolates to CD36, whereas other parasite isolates appeared to interact
directly with CD36. Thus, cytoadherence under physiological flow
conditions may be mediated by multiple IRBC ligands that interact with
different adhesion molecules in a cooperative fashion. These findings
underscore the complexity of the interactions betweeen IRBC and
vascular endothelium.
Blood, Vol. 91 No. 12 (June 15), 1998:
pp. 4803-4809
© 1998 by The American Society of Hematology.
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