Plasmodium falciparum-infected red blood cells selected for binding to cultured syncytiotrophoblast bind to chondroitin sulfate A and induce tyrosine phosphorylation in the syncytiotrophoblast.
An important pathogenic complication of malaria during human pregnancy is sequestration of Plasmodium-infected red blood cells (iRBCs) in the placental intervillous spaces. This sequestration is thought to be mediated in part by binding of the iRBCs to receptors expressed on the syncytiotrophoblast (ST) membrane. We report here the use of a dynamic system to study the consequences of this cytoadherence on ST function using human syncytiotrophoblast and the choriocarcinoma cell line, BeWo. Laboratory isolates of Plasmodium falciparum were selected for their ability to bind to ST and used to investigate binding-induced cellular changes in the ST. Treatment of the ST cells with chondroitinase ABC suggested that the selected parasites bind predominantly to chondroitin sulfate A, but other receptors for parasite binding may be involved. Intracellular signaling in the ST induced by iRBCs binding was investigated by assessing tyrosine phosphorylation of ST proteins following iRBC binding. We demonstrate for the first time that iRBC cytoadherence to syncytiotrophoblast enhances tyrosine phosphorylation of a series of proteins in these cells. This approach will be useful in further studies of ST function in the malaria-infected placenta, the dynamics of selection of syncytiotrophoblast-binding parasites, and the identification of new receptors for parasite cytoadherence in the placenta.
Lucchi
N W
NW
Department of Infectious Diseases, College of Veterinary Medicine and Center for Tropical and Emerging Global Diseases, Medical Microbiology and Parasitology, 501 DW Brooks Dr, University of Georgia, Athens, GA 30602, USA.
Koopman
R
R
Peterson
D S
DS
Moore
J M
JM
D000328:Adult; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation; D045744:Cell Line, Tumor / Q000166:cytology; D002478:Cells, Cultured; D019765:Chondroitin ABC Lyase / Q000494:pharmacology; D002809:Chondroitin Sulfates / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology* / Q000502:physiology; D005260:Female; D006801:Humans; D010766:Phosphorylation; D010770:Phosphotransferases; D010920:Placenta / Q000469:parasitology*; D010963:Plasmodium falciparum; D011247:Pregnancy; D012641:Selection, Genetic; D015398:Signal Transduction; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D014443:Tyrosine; D002809:Chondroitin Sulfates; D010770:Phosphotransferases; D019765:Chondroitin ABC Lyase