Differential binding of clonal variants of Plasmodium falciparum to allelic forms of intracellular adhesion molecule 1 determined by flow adhesion assay

Adhesion of Plasmodium falciparum-infected erythrocytes to the endothelial ligand intercellular adhesion molecule 1 (ICAM-1) has been implicated in th e pathogenesis of cerebral malaria, Recently, a high-frequency coding polym orphism in the N-terminal domain of ICAM-1 (ICAM-1(Kilifi)) that is associa ted with susceptibility to cerebral disease in Kenya has been described. Pr eliminary static adhesion assays suggested that two different selected P. f alciparum lines, ITO4-A4 (A4) and ItG-ICAM (ItG), have different properties of binding to the natural variant proteins ICAM-1 and ICAM-1(Kilifi). Usin g a how adhesion assay system, we have confirmed differences between the tw o lines in binding of parasitized erythrocytes to the variant ICAM-1 protei ns. Total adhesion of ItG-infected erythrocytes to ICAM-1 and ICAM-1(Kilifi ) is greater than that of A4-infected erythrocytes, and erythrocytes infect ed by both parasite strains shaw reduced binding to ICAM-1(Kilifi). However , under these physiologically relevant flow conditions, we have shown diffe rences between A4 and ItG strains in dynamic rolling behavior on ICAM-1(Kil ifi). The percentage of erythrocytes infected with A4 that roll on both ICA M-1 and ICAM-1(Kilifi) is greater than that of those infected with ItG. Als o, the rolling velocity of A4-infected erythrocytes on ICAM-1(Kilifi) is ma rkedly increased compared to that on ICAM-1, in contrast to the rolling vel ocity of ItG-infected erythrocytes, which is similar on both proteins. Thes e findings suggest that different parasite lines can vary in their avidity for the same host Ligand, which may have important consequences for the pat hophysiology of P. falciparum malaria.