The adhesion of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate A is mediated by P. falciparum erythrocyte membrane protein 1 - PubMed (original) (raw)

The adhesion of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate A is mediated by P. falciparum erythrocyte membrane protein 1

J C Reeder et al. Proc Natl Acad Sci U S A. 1999.

Abstract

Chondroitin sulfate A (CSA) is an important receptor for the sequestration of Plasmodium falciparum in the placenta, but the parasite ligand involved in adhesion has not previously been identified. Here we report the identification of a var gene transcribed in association with binding to CSA and present evidence that the P. falciparum erythrocyte membrane protein 1 product of the gene is the parasite ligand mediating CSA binding. Description of this gene and the implication of P. falciparum erythrocyte membrane protein 1 as the parasite ligand paves the way to a more detailed understanding of the pathogenesis of placental infection and potential therapeutic strategies targeting the interaction.

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Figures

Figure 1

Figure 1

A differentially expressed var gene associated with CSA binding was detected and sequenced. (a) Degenerate universal primers amplified a var gene DBL3 region from genomic DNA of parent and selected line, and from cDNA only in the CSA binding line. The related EBA-175 gene also was amplified under these conditions. (b) The differential expression of the cDNA transcript was confirmed with sequence specific primers. (c) Full-length sequence was obtained for a _var_-CS2 gene, including three DBL domains. The approximate positions of the primers used to generate a gene-specific probe are marked with arrows. SVL, sequence of variable length. The lines below the gene represent nine different regions that were expressed as fusion proteins and to which rabbit antisera were raised.

Figure 2

Figure 2

Antibody to recombinant fusion proteins demonstrates that a different form of PfEMP1 is expressed in the CSA selected line. (a) Western blot from a reducing PAGE probed with the conserved anti-ATS affinity purified serum showing size differences in PfEMP1. (b) Western blot from a nonreducing PAGE probed with anti-DBL4 serum differentiates between CS2 and FAF-EA8 PfEMP1.

Figure 3

Figure 3

Antisera to the recombinant _var_-CS2 CIDR and DBL3 domains significantly inhibit the binding of CS2 to CSA, when compared with DBL1, DBL4, or ATS. The bars represent the mean (±SEM) numbers of CS2-parasitized erythrocytes binding per mm2 to immobilized CSA, determined by triplicate assays performed on four separate occasions.

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References

    1. Aikawa M, Iseki M, Barnwell J W, Taylor D, Oo M M, Howard R J. Am J Trop Med Hyg. 1990;43:30–37. - PubMed
    1. Bulmer J N, Rasheed F N, Francis N, Morrison L, Greenwood B M. Histopathology. 1993;22:211–218. - PubMed
    1. Barnwell J W, Asch A S, Nachman R L, Yamaya M, Aikawa M. J Clin Invest. 1989;84:765–772. - PMC - PubMed
    1. Ockenhouse C F, Tandon N N, Magowan C, Jamieson G A, Chulay J D. Science. 1989;243:1469–1471. - PubMed
    1. Berendt A R, Simmons D L, Tansey J, Newbold C I, Marsh K. Nature (London) 1989;341:57–59. - PubMed

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