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  • Title: Plasmodium falciparum: involvement of additional receptors in the cytoadherence of infected erythrocytes to microvascular endothelial cells.
    Author: Xiao L, Yang C, Dorovini-Zis K, Tandon NN, Ades EW, Lal AA, Udhayakumar V.
    Journal: Exp Parasitol; 1996 Oct; 84(1):42-55. PubMed ID: 8925881.
    Abstract:
    The involvement of additional ligands in the cytoadhesion of PRBC to endothelial cells was studied by the use of human microvascular endothelial cells (HMEC-1), brain microvascular endothelial cells (HBEC-51), umbilical vein endothelial (HUVEC), and C32 melanoma cells as well as soluble CD36, ICAM-1, and thrombospondin in the adhesion assays. Immunostaining showed that ICAM-1 and thrombospondin were expressed by all cell lines, whereas CD36 and VCAM-1 were expressed constitutively only by C32 melanoma cells and HBEC-51, respectively; none of these cells had basal expression of E-selectin. Bindings of the parental HB3 parasite strain to HMEC-1 and HUVEC were higher than that to HBEC-51 and C32 melanoma cells. Selections by panning the parental HB3 through HMEC-1 (HB3EC-6 line) or C32 melanoma cells (HB3C32-6 to HMEC-1 was higher than that to C32 melanoma cells. Antibody or peptide blockade against CD36, ICAM-1, and thrombospondin or preincubation of target cells with TNF-alpha and IFN-gamma did not significantly alter the binding intensity of HB3EC-6 to HMEC-1 and HB3C32-6 to C32 melanoma cells. Preincubation of HMEC-1 with IL-4, however, reduced its binding with HB3EC-6. In vitro selection did not enhance the binding of PRBC to plate-bound CD36 or thrombospondin; binding to ICAM-1 was negligible. The binding of both selected lines was inhibited by dextran sulfate and sulfatides, but not by chondroitin sulfate A. These results suggested that in addition to CD36 and thrombospondin, sulfated glycoconjugates were probably concurrently utilized by these PRBC as receptors. Experiments with freshly isolated Kenyan parasites indicated that they also exhibited a similar mechanism of binding to endothelial cells.
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