Adhesion of normal and Plasmodium falciparum ring-infected erythrocytes to endothelial cells and the placenta involves the rhoptry-derived ring surface protein-2

Blood. 2003 Jun 15;101(12):5025-32. doi: 10.1182/blood-2002-12-3710. Epub 2003 Feb 27.


Recent findings have challenged the current view of Plasmodium falciparum (P falciparum) blood-stage biology by demonstrating the cytoadhesion of early ring-stage-infected erythrocytes (rIEs) to host endothelial cells and placental syncytiotrophoblasts. The adhesion of rIEs was observed only in parasites that bind to the placenta via chondroitin sulfate A (CSA). In this work, a panel of mouse monoclonal antibodies (mAbs) that specifically inhibit cytoadhesion of rIEs but not of mature IEs was generated The previously described ring surface protein 2 (RSP-2), a 42-kDa protein, was identified as the target of the ring-stage-specific mAbs. Time course surface fluorescence experiments revealed a short overlap (approximately 4 hours) of expression between RSP-2 and P falciparum erythrocyte membrane protein 1 (PfEMP1). Their consecutive expression enables IEs to adhere to endothelial cells during the entire blood-stage cycle. During this study, a new phenotype was detected in parasite cultures, the adhesion of normal erythrocytes (nEs) to endothelial cells. All adherent nEs were coated with RSP-2. Immunolocalization studies show that RSP-2 is a rhoptry-derived protein that is discharged onto the erythrocyte membrane during contact with merozoites. Our results identify RSP-2 as a key molecule in sequestration of young blood-stage forms and nEs to endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Cell Adhesion*
  • Endothelium, Vascular / cytology*
  • Erythrocytes / parasitology*
  • Erythrocytes / physiology
  • Fluorescent Antibody Technique
  • Hemorheology
  • Humans
  • Immunosorbent Techniques
  • Placenta / cytology*
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / growth & development*
  • Protozoan Proteins / blood
  • Protozoan Proteins / immunology
  • Protozoan Proteins / physiology*


  • Antibodies, Monoclonal
  • Protozoan Proteins
  • erythrocyte membrane protein 1, Plasmodium falciparum
  • rhoptry-associated antigen-2, Plasmodium