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Prepublished online as a Blood First Edition Paper on January 16, 2003; DOI 10.1182/blood-2002-08-2654. This Article Full Text (PDF) All Versions of this Article: 2002-08-2654v1 101/10/4189    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lew, V. L Articles by Ginsburg, H. Search for Related Content PubMed PubMed Citation Articles by Lew, V. L Articles by Ginsburg, H. Social Bookmarking                   What's this? Submitted August 29, 2002 Accepted January 8, 2003 Excess hemoglobin digestion and the osmotic stability of Plasmodium falciparum-infected red blood cells Virgilio L Lew*, Teresa Tiffert, and Hagai Ginsburg Department of Physiology, University of Cambridge, Cambridge, United Kingdom Institute of Life Sciences, Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel * Corresponding author; email: VLL1{at}cam.ac.uk. During their asexual reproduction cycle (~ 48 h) in human red cells Plasmodium falciparum parasites consume most of the host cell hemoglobin, far more than they require for protein biosynthesis. They also induce a large increase in the permeability of the host cell plasma membrane to allow for an increased traffic of nutrients and waste products. Why do the parasites digest hemoglobin in such excess? And how can infected red cells retain their integrity for the duration of the asexual cycle when comparably permeabilized uninfected cells hemolyse earlier?To address these questions we encoded the multiplicity of factors known to influence host cell volume in a mathematical model of the homeostasis of a parasitised red cell. The predicted volume changes were subjected to thorough experimental tests by monitoring the stage-related changes in the osmotic fragility of infected red cell populations. The results confirmed the model predictions of biphasic volume changes comprising transient shrinkage of cells infected with young trophozoites followed by continuous volume increase to about 10 % below the critical hemolytic volume of ~ 150 fL by the end of the asexual cycle. Analysis of these results and of additional model predictions demonstrated that the osmotic stability of infected red cells can be preserved only by a large reduction in impermeant solute concentration within the host cell compartment. Thus, excess hemoglobin consumption represents an essential evolutionary strategy to prevent the premature hemolysis of the highly permeabilized infected red cell. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Dalal and M. Klemba Roles for Two Aminopeptidases in Vacuolar Hemoglobin Catabolism in Plasmodium falciparum J. Biol. Chem., December 7, 2007; 282(49): 35978 - 35987. [Abstract] [Full Text] [PDF] G. Bouyer, S. Egee, and S. L. Y. Thomas Toward a unifying model of malaria-induced channel activity PNAS, June 26, 2007; 104(26): 11044 - 11049. [Abstract] [Full Text] [PDF] H. M. Staines, S. Ashmore, H. Felgate, J. Moore, T. Powell, and J. C. 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