title: P. falciparum isolate-specific distinct patterns of induced apoptosis in pulmonary and brain endothelial cells.
abstract: The factors implicated in the transition from uncomplicated to severe clinical malaria such as pulmonary oedema and cerebral malaria remain unclear. It is known that alterations in vascular integrity due to endothelial cell (EC) activation and death occur during severe malaria. In this study, we assessed the ability of different P. falciparum clinical isolates to induce apoptosis in ECs derived from human lung and brain. We observed that induction of EC apoptosis was sensitive to the environmental pH and required direct contact between the parasite and the cell, though it was not correlated to the ability of the parasite to cytoadhere. Moreover, the extent of induced apoptosis in the two EC types varied with the isolate. Analysis of parasite genes transcript led us to propose that the activation of different pathways, such as Plasmodium apoptosis-linked pathogenicity factors (PALPF), PALPF-2, PALPF-5 and PF11_0521, could be implied in EC death. These observations provide an experimental framework to decipher the molecular mechanism implicated in the genesis of severe malaria.
authors.affiliation: Université Pierre et Marie Curie-Paris 6, UMRS 945, Paris, France; Institut National de la Santé et de la Recherche Médicale, UMRS 945, Paris, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: N'Dilimabaka
authors.affiliation: Université Pierre et Marie Curie-Paris 6, UMRS 945, Paris, France; Institut National de la Santé et de la Recherche Médicale, UMRS 945, Paris, France.
authors.forename: Zacharie
authors.initials: Z
authors.lastname: Taoufiq
authors.affiliation: Université Pierre et Marie Curie-Paris 6, UMRS 945, Paris, France; Institut National de la Santé et de la Recherche Médicale, UMRS 945, Paris, France.
authors.forename: Sergine
authors.initials: S
authors.lastname: Zougbédé
authors.affiliation: Institut Pasteur, Unité d'Immunologie Moléculaire des Parasites, CNRS URA 2581, Paris, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Bonnefoy
authors.affiliation: Université Pierre et Marie Curie-Paris 6, UMRS 945, Paris, France; Institut National de la Santé et de la Recherche Médicale, UMRS 945, Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Lorthiois
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Pierre Oliver
authors.initials: PO
authors.lastname: Couraud
authors.affiliation: Université Pierre et Marie Curie-Paris 6, UMRS 945, Paris, France; Institut National de la Santé et de la Recherche Médicale, UMRS 945, Paris, France.
authors.forename: Angelita
authors.initials: A
authors.lastname: Rebollo
authors.affiliation: Université Pierre et Marie Curie-Paris 6, UMRS 945, Paris, France; Institut National de la Santé et de la Recherche Médicale, UMRS 945, Paris, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Snounou
authors.affiliation: Université Pierre et Marie Curie-Paris 6, UMRS 945, Paris, France; Institut National de la Santé et de la Recherche Médicale, UMRS 945, Paris, France; Laboratoire de Parasitologie-Mycologie, AP-HP, Hôpital Pitié Salpêtrière, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
authors.affiliation: Université Pierre et Marie Curie-Paris 6, UMRS 945, Paris, France; Institut National de la Santé et de la Recherche Médicale, UMRS 945, Paris, France.
authors.forename: Alicia
authors.initials: A
authors.lastname: Moreno Sabater
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000469:parasitology*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000469:parasitology*; D006801:Humans; D008168:Lung / Q000469:parasitology*; D016778:Malaria, Falciparum / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000302:isolation & purification*