Modeling of Plasmodium falciparum - Infected erythrocyte cytoadhesion in microvascular conditions: Chondroitin-4-sulfate binding, a competitive phenotype

Abstract

Although chondroitin-4-sulfate (CSA) is expressed throughout the microvasculature and CSA-binding infected erythrocytes (IECSA) cytoadhere to lung and brain endothelial cells and sequester in male Saimiri sciureus, this phenotype seems to be dependent on the presence of a placenta to develop. This contradiction was investigated by modeling the interactions and cytoadhesion parameters in the microvasculature. Mixtures of IEs interacting with CSA, CD36, or intercellular adhesion molecule 1 were incubated with endothelial cells expressing the corresponding receptors, at physiological pH, under flow conditions. By use of suspensions composed of equal proportions of the phenotypes, cytoadhesion of ∼10 times as many IECSA as of any other IE tested was observed. Adherent IECSA resisted microvascular wall shear stresses 3-15 times more effectively than did the others. These results, which require confirmation with field isolates, demonstrate that the CSA phenotype is competitive and are consistent with this phenotype initiating microvessel occlusion and with CSA-mediated sequestration in microvessel conditions.