Adhesion of malariainfected red blood cells to chondroitin sulfate A under flow conditions

Adhesion of parasitized red blood cells (PRBCs) to microvas-cular endothelial cells (ECs) is a distinctive feature of Plasmo-dium falciparum malaria and is a central event in the devel-opment 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 adhe-sion 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 URING INFECTION WITH Plasmodium falciparum, D parasitized red blood cells (PRBCs) adhere to endothe-lial cells (ECs) and accumulate in the microvasculature of various organs. This phenomenon, which is known as se-questration,’. ’ is complex at the cellular level because of the potential involvement of a number of EC-expressed adhesion molecules including intercellular adhesion molecule- 1 (ICAM-l), CD36, thrombospondin (TSP), vascular cell ad-hesion molecule-1 (VCAM-l), and E-selectin. ’ Recently, chondroitin sulfate A (CSA), a glycosaminoglycan associ-ated with the EC surface, has also been added to this list.?‘ Studies to identify the molecules to which PRBCs can adhere have been performed exclusively using cultured cells or puri-fied proteins in highly artificial assays under conditions that ignore the shear forces exerted by flowing blood. A good way to identify those receptors, or combination of receptors, that actually operate in vivo is by the use of in vitro flow systems that can accurately mimic the hemody-namic forces that act on PRBCs in the circulation. ’ Once shear forces are operative, it becomes apparent that different receptors mediate quantitatively and qualitatively different forms of adhesion. For example, we have previously shown that, when adhesion was tested at shear stresses typical of those for postcapillary venules, PRBCs that adhered to CD36 or TSP remained stationary, whereas those adhering t