title: Adhesion of Plasmodium falciparum infected erythrocytes in ex vivo perfused placental tissue: a novel model of placental malaria.
abstract: Placental malaria occurs when Plasmodium falciparum infected erythrocytes sequester in the placenta. Placental parasite isolates bind to chondroitin sulphate A (CSA) by expression of VAR2CSA on the surface of infected erythrocytes, but may sequester by other VAR2CSA mediated mechanisms, such as binding to immunoglobulins. Furthermore, other parasite antigens have been associated with placental malaria. These findings have important implications for placental malaria vaccine design. The objective of this study was to adapt and describe a biologically relevant model of parasite adhesion in intact placental tissue.
  
  
  
  The ex vivo placental perfusion model was modified to study adhesion of infected erythrocytes binding to CSA, endothelial protein C receptor (EPCR) or a transgenic parasite where P. falciparum erythrocyte membrane protein 1 expression had been shut down. Infected erythrocytes expressing VAR2CSA accumulated in perfused placental tissue whereas the EPCR binding and the transgenic parasite did not. Soluble CSA and antibodies specific against VAR2CSA inhibited binding of infected erythrocytes.
  
  
  
  The ex vivo model provides a novel way of studying receptor-ligand interactions and antibody mediated inhibition of binding in placental malaria.
authors.affiliation: Centre for Medical Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and at Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark. cpeh@sund.ku.dk.
authors.forename: Caroline
authors.initials: C
authors.lastname: Pehrson
authors.affiliation: Section of Environmental Health, Department of Public Health, University of Copenhagen, Øster Farimagsgade 5A, 1353, Copenhagen, Denmark.
authors.forename: Line
authors.initials: L
authors.lastname: Mathiesen
authors.affiliation: Centre for Medical Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and at Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
authors.forename: Kristine K
authors.initials: KK
authors.lastname: Heno
authors.affiliation: Centre for Medical Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and at Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
authors.forename: Ali
authors.initials: A
authors.lastname: Salanti
authors.affiliation: Centre for Medical Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and at Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Resende
authors.affiliation: Department of Microbiology and Molecular Genetics, The Institute for Medical Research Israel-Canada, The Kuvin Center for the Study of Infectious and Tropical Diseases, The Hebrew University-Hadassah Medical School, 91120, Jerusalem, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Dzikowski
authors.affiliation: Department of Obstetrics, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Damm
authors.affiliation: Division of Obstetrics and Gynecology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Hansson
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University and Veterans Affairs Medical Center, Cleveland, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: King
authors.affiliation: Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
authors.forename: Henning
authors.initials: H
authors.lastname: Schneider
authors.affiliation: Centre for Medical Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and at Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Wang
authors.affiliation: Centre for Medical Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and at Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lavstsen
authors.affiliation: Centre for Medical Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and at Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
authors.forename: Thor G
authors.initials: TG
authors.lastname: Theander
authors.affiliation: Section of Environmental Health, Department of Public Health, University of Copenhagen, Øster Farimagsgade 5A, 1353, Copenhagen, Denmark.
authors.forename: Lisbeth E
authors.initials: LE
authors.lastname: Knudsen
authors.affiliation: Centre for Medical Parasitology at Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and at Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark. mortenn@sund.ku.dk.
authors.forename: Morten A
authors.initials: MA
authors.lastname: Nielsen
mesh_terms: D002448:Cell Adhesion; D004912:Erythrocytes / Q000469:parasitology* / Q000502:physiology*; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology / Q000473:pathology*; D008962:Models, Theoretical; D010920:Placenta / Q000469:parasitology* / Q000473:pathology*; D010922:Placenta Diseases / Q000469:parasitology / Q000473:pathology*; D010963:Plasmodium falciparum; D011247:Pregnancy
keywords: Placental malaria; Placental perfusion; VAR2CSA