PLASMODIUM-FALCIPARUM - INVOLVEMENT OF ADDITIONAL RECEPTORS IN THE CYTOADHERENCE OF INFECTED ERYTHROCYTES TO MICROVASCULAR ENDOTHELIAL-CELLS

The involvement of additional ligands in the cytoadhesion of PRBC to e ndothelial cells was studied by the use of human microvascular endothe lial cells (HMEC-1), brain microvascular endothelial cells (HBEC-51), umbilical vein endothelial cells (HUVEC), and C32 melanoma cells as we ll as soluble CD36, ICAM-1, and thrombospondin in the adhesion assays. Immunostaining showed that ICAM-1 and thrombospondin were expressed b y all eel lines, whereas CD36 and VCAM-1 were expressed constitutively only by C32 melanoma cells and HBEC-5T, respectively; none of these c ells had basal expression of E-selectin. Bindings of the parental HB3 parasite strain to HMEC-1 and HUVEC were higher man that to HBEC-5I an d C32 melanoma cells. Selections by panning the parental HB3 through H MEC-1 (HB3EC-6 line) or C32 melanoma cells (HB3C32-6 line) six times i ncreased bindings by more than 10-fold, but the binding of HB3C32-6 to HMEC-1 was higher than that to C32 melanoma cells. Antibody or peptid e blockade against CD36, ICAM-1, and thrombospondin or preincubation o f target cells with TNF-alpha and IFN-gamma did not significantly alte r the binding intensity of HB3EC-6 to HMEC-1 and HB3C32-6 to C32 melan oma cells. Preincubation of HMEC-1 with IL-4, however, reduced its bin ding with HB3EC-6. In vitro selection did not enhance the binding of P RBC to plate bound CD36 or thrombospondin; binding to ICAM-1 was negli gible. The binding of both selected lines was inhibited by dextran sul fate and sulfatides, but not by chondroitin sulfate A. These results s uggested that in addition to CD36 and thrombospondin, sulfated glycoco njugates were probably concurrently utilized by these PRBC as receptor s. Experiments with freshly isolated Kenyan parasites indicated that t hey also exhibited a similar mechanism of binding to endothelial cells . (C) 1996 Academic Press, Inc.