title: Platelets reorient Plasmodium falciparum-infected erythrocyte cytoadhesion to activated endothelial cells.
abstract: Severe malaria is characterized by the sequestration of Plasmodium falciparum-infected erythrocytes (IEs). Because platelets can affect tumor necrosis factor (TNF)-activated endothelial cells (ECs), we investigated their role in the sequestration of IEs, using IEs that were selected because they can adhere to endothelial CD36 (IE(CD36)), a P. falciparum receptor that is expressed on platelets. The results of coincubation studies indicated that platelets can induce IE(CD36) binding to CD36-deficient brain microvascular ECs. This induced cytoadhesion resisted physiological shear stress, was increased by EC stimulation with TNF, and was abolished by anti-CD36 monoclonal antibody. Immunofluorescence and scanning electron microscopy results showed that platelets serve as a bridge between IEs and the surface of ECs and may therefore provide receptors for adhesion to microvascular beds that otherwise lack adhesion receptors. This novel mechanism of cytoadhesion may reorient the sequestration of different parasite phenotypes and play an important role in the pathogenesis of severe malaria.
authors.affiliation: Unité de Parasitologie Expérimentale, Equipe d'Accueil 3282, Institut Fédératif de Recherche 48, Faculty of Medicine, Université de la Méditerranée, Marseille, France.
authors.forename: Samuel Crocodile
authors.initials: SC
authors.lastname: Wassmer
authors.forename: Catherine
authors.initials: C
authors.lastname: Lépolard
authors.forename: Boubacar
authors.initials: B
authors.lastname: Traoré
authors.forename: Bruno
authors.initials: B
authors.lastname: Pouvelle
authors.forename: Jürg
authors.initials: J
authors.lastname: Gysin
authors.forename: Georges Emile
authors.initials: GE
authors.lastname: Grau
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D018955:CD36 Antigens / Q000502:physiology; D019013:CD40 Antigens / Q000502:physiology; D002448:Cell Adhesion; D002450:Cell Communication; D042783:Endothelial Cells / Q000166:cytology*; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D010963:Plasmodium falciparum / Q000502:physiology*; D012453:Saimiri
chemical_list: D018955:CD36 Antigens; D019013:CD40 Antigens