Placenta cryosections for study of the adhesion of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate A in flow conditions.
The adhesion of Plasmodium falciparum-infected erythrocytes (IEs) to chondroitin-4-sulfate (CSA) via the PfEMP1-CSA parasite ligand domain is correlated with placental malaria in primigravidae. The recent identification of parasite genes encoding CSA adhesion molecules and the development of pan-reactive monoclonal antibodies against the Pf(CSA) ligand have opened up new avenues for the development of anti-IE sequestration therapies for the prevention of placental malaria. A model closely mimicking placental sequestration of IEs during pregnancy is needed for the preclinical and clinical evaluation of candidate molecules for the induction of antibodies that could protect pregnant women from placental malaria. We found that normal placenta cryosections were a specific and highly consistent support for the binding of IEs to CSA in flow conditions under physiological conditions. This model makes possible the quantitative and qualitative analysis of IE adhesion. We identified distinct CSA-binding phenotypes within the FCR3(CSA)-selected parasites in flow analyses, but not in static analyses. We also analyzed inhibitors of placental parasite binding such as soluble CSA and antibodies directed against the Pf(CSA) ligand. Our data demonstrate that placenta cryosections could be used to standardize assays between laboratories, potentially advancing the development of therapies against placental malaria.
Avril
Marion
M
Unité de Parasitologie Expérimentale URA IPP/UNIV-MED EA 3282, IFR 48, Faculté de Médecine, Université de la Méditerranée, 27 Boulevard Jean Moulin, 13385 Marseille cedex 5, France.
Traoré
Boubacar
B
Costa
Fabio T M
FT
Lépolard
Catherine
C
Gysin
Jürg
J
D000818:Animals; D001706:Biopsy; D002448:Cell Adhesion; D002809:Chondroitin Sulfates / Q000378:metabolism* / Q000494:pharmacology; D016616:Cryoultramicrotomy; D004912:Erythrocytes / Q000469:parasitology*; D005260:Female; D006801:Humans; D010920:Placenta / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000502:physiology*; D011247:Pregnancy; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015203:Reproducibility of Results; D012995:Solubility
D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D002809:Chondroitin Sulfates