ADHESION OF MALARIA-INFECTED RED-BLOOD-CELLS TO CHONDROITIN SULFATE-AUNDER FLOW CONDITIONS

Adhesion of parasitized red blood cells (PRBCs) to microvascular endot helial cells (ECs) is a distinctive feature of Plasmodium falciparum m alaria and isa central event in the development of life-threatening co mplications such as cerebral malaria. PRBCs adhere to several EC-expre ssed molecules in vitro, but the relative importance of these interact ions 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 GSA in vit ro using a parallel-plate flow chamber. Under controlled flow conditio ns, PRBCs adhered to CSA in a concentration-dependent manner at wall-s hear stresses Lap to 0.2 Pa, a value that is within the physiological range for venules. Once adhered, PRBCs remained stationary (rather tha n rolling) and continued to remain stationary even when the wall-shear stress was raised to supravenular levels. The adhesive interaction wa s strong and a proportion of adherent PRBCs could withstand detachment at stresses up to 2.5 Pa. Soluble CSA at pharmacological concentratio ns prevented adhesion of flowing PRBCs in a concentration-dependent ma nner but failed to reverse established adhesion. Adhesion of PRBCs to CSA could contribute to the pathogenesis of malaria, and soluble CSA m ay have a useful therapeutic effect. (C) 1996 by The American Society of Hematology.