OPTIMIZATION AND INHIBITION OF THE ADHERENT ABILITY OF PLASMODIUM-FALCIPARUM-INFECTED ERYTHROCYTES

The vast majority of the 1-2 million malaria associated deaths that oc cur each year are due to anemia and cerebral malaria (the attachment o f erythrocytes containing mature forms of Plasmodium falciparum to the endothelial cells that line the vascular beds of the brain). A ''mode l system'' for the study of cerebral malaria employs amelanotic melano ma cells as the ''target'' cells in an in vitro cytoadherence assay. U sing this model system we determined that the optimum pH for adherence is 6.6 to 6.8, that high concentrations of Ca2+ (50 mM) result in inc reased levels of binding, and that the type of buffer used influences adherence (Bis Tris> MOPS> HEPES> PIPES). We also observed that the ab ility of infected erythrocytes to cyloadhere varied from (erythrocyte) donor to donor. We have produced murine monoclonal antibodies against P. falciparum-infected red cells which recognize modified forms of hu man band 3; these inhibit the adherence of infected erythrocytes to me lanoma cells in a dose-responsive fashion. Antimalarials (chloroquine, quinacrine, mefloquine, artemisinin), on the other hand, affected adh erence in an indirect fashion i.e. since cytoadherence is due, in part , to the presence of knobs on the surface of the infected erythrocyte, and knob formation is dependent on intracellular parasite growth, whe n plasmodial development is inhibited so is knob production, and conse quently adherence is ablated.