Adhesion of Malaria-Infected Red Blood Cells to Chondroitin Sulfate A Under Flow Conditions

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 v...

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Bibliographic Details
Published in:Blood 1996-11, Vol.88 (10), p.4040-4044
Main Authors: Cooke, Brian M., Rogerson, Stephen J., Brown, Graham V., Coppel, Ross L.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cell Adhesion
Chondroitin Sulfates - metabolism
Dose-Response Relationship, Drug
Erythrocytes - parasitology
Erythrocytes - pathology
Hemorheology
Human protozoal diseases
Humans
Infectious diseases
Malaria
Malaria - blood
Malaria - parasitology
Medical sciences
Parasitic diseases
Protozoal diseases
Stress, Mechanical
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V88.10.4040.bloodjournal88104040