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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1192-1199. Prepublished online as a Blood First Edition Paper on October 6, 2005; DOI 10.1182/blood-2005-08-3460. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-08-3460v1 107/3/1192    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Evans, K. J. Articles by Schofield, L. Search for Related Content PubMed PubMed Citation Articles by Evans, K. J. Articles by Schofield, L. Related Collections Immunobiology Red Cells Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Severe malarial anemia of low parasite burden in rodent models results from accelerated clearance of uninfected erythrocytes Krystal J. Evans, Diana S. Hansen, Nico van Rooijen, Lynn A. Buckingham, and Louis Schofield From The Walter and Eliza Hall Institute of Medical Research (WEHI), Parkville, Victoria, Australia; and the Department of Molecular Cell Biology, Vrije Universiteit, Amsterdam, the Netherlands. Severe malarial anemia (SMA) is the most frequent life-threatening complication of malaria and may contribute to the majority of malarial deaths worldwide. To explore the mechanisms of pathogenesis, we developed a novel murine model of SMA in which parasitemias peaked around 1.0% of circulating red blood cells (RBCs) and yet hemoglobin levels fell to 47% to 56% of baseline. The severity of anemia was independent of the level of peak or cumulative parasitemia, but was linked kinetically to the duration of patent infection. In vivo biotinylation analysis of the circulating blood compartment revealed that anemia arose from accelerated RBC turnover. Labeled RBCs were reduced to 1% of circulating cells by 8 days after labeling, indicating that the entire blood compartment had been turned over in approximately one week. The survival rate of freshly transfused RBCs was also markedly reduced in SMA animals, but was not altered when RBCs from SMA donors were transferred into naive recipients, suggesting few functional modifications to target RBCs. Anemia was significantly alleviated by depletion of either phagocytic cells or CD4+ T lymphocytes. This study demonstrates that immunologic mechanisms may contribute to SMA by promoting the accelerated turnover of uninfected RBCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Malaria: death and disappearing erythrocytes John W. Barnwell Blood 2006 107: 854-855. [Full Text] [PDF] This article has been cited by other articles: N. Thawani, M. Tam, and M. M. Stevenson STAT6-mediated suppression of erythropoiesis in an experimental model of malarial anemia Haematologica, February 1, 2009; 94(2): 195 - 204. [Abstract] [Full Text] [PDF] A. L. Graham Ecological rules governing helminth microparasite coinfection PNAS, January 15, 2008; 105(2): 566 - 570. [Abstract] [Full Text] [PDF] Y. Miyazaki, M. Bunting, D. M. Stafforini, E. S. Harris, T. M. McIntyre, S. M. Prescott, V. S. Frutuoso, F. C. Amendoeira, D. de Oliveira Nascimento, A. Vieira-de-Abreu, et al. Integrin {alpha}D 2 Is Dynamically Expressed by Inflamed Macrophages and Alters the Natural History of Lethal Systemic Infections J. Immunol., January 1, 2008; 180(1): 590 - 600. [Abstract] [Full Text] [PDF] A. W. Pawluczkowycz, M. A. Lindorfer, J. N. Waitumbi, and R. P. Taylor Hematin Promotes Complement Alternative Pathway-Mediated Deposition of C3 Activation Fragments on Human Erythrocytes: Potential Implications for the Pathogenesis of Anemia in Malaria J. Immunol., October 15, 2007; 179(8): 5543 - 5552. [Abstract] [Full Text] [PDF] A. A. Lamikanra, D. Brown, A. Potocnik, C. Casals-Pascual, J. Langhorne, and D. J. Roberts Malarial anemia: of mice and men Blood, July 1, 2007; 110(1): 18 - 28. [Abstract] [Full Text] [PDF]

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