PROMISCUITY OF CLINICAL PLASMODIUM-FALCIPARUM ISOLATES FOR MULTIPLE ADHESION MOLECULES UNDER FLOW CONDITIONS

The central pathologic process in severe Plasmodium falciparum malaria is the cytoadherence of parasitized erythrocytes to capillary and pos tcapillary venular endothelium, with resultant tissue hypoxia, metabol ic disturbances, and multiorgan dysfunction, The molecular basis of th is process has been studied extensively using static adhesion assays, In the present study, we determined whether infected red blood cells ( IRBC) from clinical parasite isolates would roll and adhere on CD36, I CAM-1, E-selectin, P-selectin, and VCAM-1 using a laminar flow system that allowed for the direct visualization of IRBC-substratum interacti ons, The results indicate that IRBC could tether and roll on CD36, ICA M-1, P-selectin, and VCAM-1 in a shear-dependent fashion, but signific ant adhesion was restricted to CD36, There was no interaction with E-s electin. When both CD36 and ICAM-1 were expressed on the same cellular substratum such as C32 melanoma cells, adhesion was significantly gre ater than when CD36 was present alone, The adhesive interactions were different from those between leukocytes and the same adhesion molecule s, Furthermore, IRBC rolling on P-selectin and VCAM-1 was not inhibita ble by Abs that entirely prevented leukocyte-receptor interactions. Th ese findings suggest that cytoadherence under physiologic conditions m ay be a multistep process similar to that involved in the recruitment of a number of different cell types, Further elucidation of the molecu lar basis of these novel interactions is crucial for the development o f therapeutic interventions aimed at inhibiting or reversing the proce ss.