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 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.
Department of Microbiology, Monash University, Clayton, Victoria, Australia.
B M
BM
Cooke
S J
SJ
Rogerson
G V
GV
Brown
R L
RL
Coppel
D002448:Cell Adhesion; D002809:Chondroitin Sulfates / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000469:parasitology* / Q000473:pathology; D018056:Hemorheology; D006801:Humans; D008288:Malaria / Q000097:blood* / Q000469:parasitology; D013314:Stress, Mechanical
D002809:Chondroitin Sulfates