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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 28, 2008 Accepted May 30, 2008 Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open micro-circulation of the human spleen Innocent Safeukui, Jean-Michel Correas, Valentine Brousse, Deborah Hirt, Guillaume Deplaine, Sebastien Mule, Mickael Lesurtel, Nicolas Goasguen, Alain Sauvanet, Anne Couvelard, Sophie Kerneis, Huot Khun, Ines Vigan-Womas, Catherine Ottone, Thierry Jo Molina, Jean-Marc Treluyer, Odile Mercereau-Puijalon, Genevieve Milon, Peter H David, and Pierre A Buffet* Molecular immunology of parasites unit, Institut Pasteur, Paris, France Radiology Department, Necker Hospital, APHP, Paris, France Pharmacology Department, Saint Vincent de Paul Hospital, APHP, Paris, France Surgery and Pathology Departments, Beaujon Hospital, APHP, Clichy, France Imaging Platform, Institut Pasteur, Paris, France Histology Unit, Institut Pasteur, Paris, France Pathology Department, Hotel Dieu Hospital, APHP, Paris, France Immunophysiology and intracellular parasitism unit, Institut Pasteur, Paris, France Parasitology and Mycology Department, Pitie-Salpetriere Hospital, APHP, Paris, France * Corresponding author; email: pabuffet{at}pasteur.fr. The current paradigm in Plasmodium falciparum malaria pathogenesis states that young, ring-infected red blood cells (rings) circulate in peripheral blood whereas mature stages are sequestered in the vasculature, thereby avoiding clearance by the spleen. Through the ex-vivo perfusion of intact human spleens we were able to examine the interaction of this unique blood-filtering organ with P. falciparum-infected red blood cells. As predicted, mature stages were rapidly retained. However, >50% 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 subsequently sequester in vital organs, influencing the risk of severe complications such as cerebral malaria or severe anaemia. 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?

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020