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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2520-2528. Prepublished online as a Blood First Edition Paper on June 25, 2008; DOI 10.1182/blood-2008-03-146779. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-03-146779v1 112/6/2520    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Safeukui, I. Articles by Buffet, P. A. Search for Related Content PubMed PubMed Citation Articles by Safeukui, I. Articles by Buffet, P. A. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open microcirculation of the human spleen Innocent Safeukui1, Jean-Michel Correas2, Valentine Brousse1, Déborah Hirt3, Guillaume Deplaine1, Sébastien Mulé2, Mickael Lesurtel4, Nicolas Goasguen4, Alain Sauvanet4, Anne Couvelard4, Sophie Kerneis5, Huot Khun6, Inès Vigan-Womas1, Catherine Ottone1, Thierry Jo Molina7, Jean-Marc Tréluyer3, Odile Mercereau-Puijalon1, Geneviève Milon8, Peter H. David1, and Pierre A. Buffet1,9 1 Molecular Immunology of Parasites Unit, CNRS URA 2581, Institut Pasteur, Paris; 2 Radiology Department, Necker Hospital, Assistance Publique des Hopitaux de Paris (APHP), Paris; 3 Pharmacology Department, Saint Vincent de Paul Hospital, APHP, Paris; 4 Surgery and Pathology Departments, Beaujon Hospital, APHP, Clichy; 5 Imaging Platform and 6 Histology Unit, Institut Pasteur, Paris; 7 Pathology Department, Hôtel Dieu Hospital, APHP, Paris; 8 Immunophysiology and Intracellular Parasitism Unit, Institut Pasteur, Paris; and 9 Parasitology & Mycology Department, Pitié-Salpêtrière Hospital, APHP, Paris, France The current paradigm in Plasmodium falciparum malaria pathogenesis states that young, ring-infected erythrocytes (rings) circulate in peripheral blood and that mature stages are sequestered in the vasculature, avoiding clearance by the spleen. Through ex vivo perfusion of human spleens, we examined the interaction of this unique blood-filtering organ with P falciparum–infected erythrocytes. As predicted, mature stages were retained. However, more than 50% of rings were also retained and accumulated upstream from endothelial sinus wall slits of the open, slow red pulp microcirculation. Ten percent of rings were retained at each spleen passage, a rate matching the proportion of blood flowing through the slow circulatory compartment established in parallel using spleen contrast-enhanced ultrasonography in healthy volunteers. Rings displayed a mildly but significantly reduced elongation index, consistent with a retention process, due to their altered mechanical properties. This raises the new paradigm of a heterogeneous ring population, the less deformable subset being retained in the spleen, thereby reducing the parasite biomass that will sequester in vital organs, influencing the risk of severe complications, such as cerebral malaria or severe anemia. Cryptic ring retention uncovers a new role for the spleen in the control of parasite density, opening novel intervention opportunities. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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