title: Characterization of human placental glycosaminoglycans and regional binding to VAR2CSA in malaria infected erythrocytes.
abstract: Placental malaria is a serious problem in sub-Saharan Africa. Young women are particular susceptible to contracting this form of malaria during their first or second pregnancy despite previously acquired immunity from past infections. Placental malaria is caused by Plasmodium falciparum parasites expressing VAR2CSA on the erythrocyte surface. This protein adheres to a low-sulfated chondroitin sulfate-A found in placental tissue causing great harm to both mother and developing fetus. In rare cases, the localization of infected erythrocytes to the placenta can even result in the vertical transmission of malaria. In an effort to better understand this infection, chondroitin sulfate was isolated from the cotyledon part of the placenta, which should be accessible for parasite adhesion, as well as two non-accessible parts of the placenta to serve as controls. The placental chondroitin sulfate structures and their VAR2CSA binding were characterized. All portions of human placenta contained sufficient amounts of the appropriate low-sulfated chondroitin sulfate-A to display high-affinity binding to a recombinant truncated VAR2CSA construct, as determined using surface plasmon resonance. The cotyledon is the only placental tissue accessible to parasites in the bloodstream, suggesting it is the primary receptor for parasite infected red blood cells.
authors.affiliation: Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic, Troy, NY, 12180, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Beaudet
authors.forename: Leandra
authors.initials: L
authors.lastname: Mansur
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Joo
authors.forename: Eyal
authors.initials: E
authors.lastname: Kamhi
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Clausen
authors.forename: Ali
authors.initials: A
authors.lastname: Salanti
authors.forename: Fuming
authors.initials: F
authors.lastname: Zhang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
mesh_terms: D000953:Antigens, Protozoan / Q000378:metabolism*; D001665:Binding Sites; D002809:Chondroitin Sulfates / Q000737:chemistry; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D005260:Female; D006025:Glycosaminoglycans / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008970:Molecular Weight; D010920:Placenta / Q000737:chemistry*; D011247:Pregnancy; D020349:Surface Plasmon Resonance
chemical_list: D000953:Antigens, Protozoan; D006025:Glycosaminoglycans; C512601:VAR2CSA protein, Plasmodium falciparum; D002809:Chondroitin Sulfates