Adhesion of normal and Plasmodium falciparum ring-infected erythrocytes to endothelial cells and the placenta involves the rhoptry-derived ring surface protein-2.
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.
Douki
Jean-Bernard Lekana
JB
Unité de Parasitologie Expérimentale, Université de la Méditerranée, France.
Sterkers
Yvon
Y
Lépolard
Catherine
C
Traoré
Boubacar
B
Costa
Fabio T M
FT
Scherf
Artur
A
Gysin
Jürg
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000166:cytology*; D004912:Erythrocytes / Q000469:parasitology* / Q000502:physiology; D005455:Fluorescent Antibody Technique; D018056:Hemorheology; D006801:Humans; D007163:Immunosorbent Techniques; D010920:Placenta / Q000166:cytology*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development*; D015800:Protozoan Proteins / Q000097:blood / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; C073168:rhoptry-associated antigen-2, Plasmodium