A RECOMBINANT PEPTIDE-BASED ON PFEMP-1 BLOCKS AND REVERSES ADHESION OF MALARIA-INFECTED RED-BLOOD-CELLS TO CD36 UNDER FLOW

During falciparum malaria infection, severe complications ensue becaus e parasitized red blood cells (PRBCs) adhere to endothelial cells and accumulate in the microvasculature. At the molecular level, adhesion i s mediated by interaction of Plasmodium falciparum erythrocyte membran e protein 1 (PfEMP-1) on the PRBC surface with receptors on the surfac e of endothelial cells, including CD36. We have shown that a recombina nt 179-residue subfragment of PfEMP-1 (rC1-2[1-179]), which encompasse s the CD36-binding region, inhibits and reverses adhesion of PRBCs to CD36 under physiologically relevant flow conditions. rC1-2[1-179] inhi bited adhesion in a concentration-dependent manner over the range 100 pM to 2 mu M, with up to 99% of adhesion blocked at the highest concen tration tested. The antiadhesive activity of rC1-2[1-179] was not stra in specific and almost totally ablated adhesion of four different para site lines. Furthermore, rC1-2[1-179] showed remarkable ability to pro gressively reverse adhesion when flowed over adherent PRBCs for 2 h. T he effect of rC1-2[1-179] was, however, specific for CD36-mediated adh esion and had no effect on adhesion mediated by CSA. Interference with binding of PRBCs to the vascular endothelium using rC1-2[1-179] or sm aller organic mimetics may be a useful therapeutic approach to amelior ate severe complications of falciparum malaria.