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Adhesion of malaria-infected red blood cells to chondroitin sulfate A under
flow conditions
BM Cooke, SJ Rogerson, GV Brown and RL Coppel
Department of Microbiology, Monash University, Clayton, Victoria,
Australia.
Adhesion of parasitized red blood cells (PRBCs) to microvascular
endothelial cells (ECs) is a distinctive feature of Plasmodium falciparum
malaria and is a central event in the development of life- threatening
complications such as cerebral malaria. PRBCs adhere to several
EC-expressed molecules in vitro, but the relative importance of these
interactions in vivo remains unclear. Chondroitin sulfate A (CSA) is the
most recent EC surface-associated molecule to be implicated in the adhesive
process. Accordingly, we have studied adhesion of PRBCs to CSA in vitro
using a parallel-plate flow chamber. Under controlled flow conditions,
PRBCs adhered to CSA in a concentration-dependent manner at wall-shear
stresses up to 0.2 Pa, a value that is within the physiological range for
venules. Once adhered, PRBCs remained stationary (rather than rolling) and
continued to remain stationary even when the wall-shear stress was raised
to supravenular levels. The adhesive interaction was strong and a
proportion of adherent PRBCs could withstand detachment at stresses up to
2.5 Pa. Soluble CSA at pharmacological concentrations prevented adhesion of
flowing PRBCs in a concentration-dependent manner but failed to reverse
established adhesion. Adhesion of PRBCs to CSA could contribute to the
pathogenesis of malaria, and soluble CSA may have a useful therapeutic
effect.
Volume 88,
Issue 10,
pp. 4040-4044,
11/15/1996
Copyright © 1996 by The American Society of Hematology
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