SEARCH:   Advanced

Blood, 15 October 2006, Vol. 108, No. 8, pp. 2569-2577. Prepublished online as a Blood First Edition Paper on June 27, 2006; DOI 10.1182/blood-2006-05-018697. This Article Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2006-05-018697v1 108/8/2569    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 Casals-Pascual, C. Articles by Roberts, D. J Search for Related Content PubMed PubMed Citation Articles by Casals-Pascual, C. Articles by Roberts, D. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 22, 2005 Accepted June 8, 2006 Suppression of erythropoiesis in malarial anemia is associated with hemozoin in vitro and in vivo Climent Casals-Pascual*, Oscar Kai, Joyce O Cheung, Senani Williams, Brett Lowe, Mike Nyanoti, Thomas N Williams, Kathryn Maitland, Malcolm Molyneux, Charles R Newton, Norbert Peshu, Suzanne M Watt, and David J Roberts National Blood Service, NHS KEMRI Centre for Geographic Medicine Coast, PO Box 230, Kilifi, Kenya Nuffield Department of Clinical Laboratory Sciences Dept. of Pathology, Faculty of Medicine,University of Kelaniya, Sri Lanka Malawi-Wellcome Trust Research Programme, Blantyre, Malawi National Blood Service Oxford Centre, NHS * Corresponding author; email: climentcasals{at}hotmail.com. Malarial anemia is a major public health problem in endemic areas and is characterized by a low reticulocyte response in the presence of life-threatening hemolysis. Although it was previously suggested that cytokines, in particular tumor necrosis factor- (TNF-), could suppress erythropoiesis, the grossly abnormal bone marrow morphology in acute, as well as in chronic malarial infection indicates that other factors may contribute to ineffective erythropoiesis. We hypothesized that the cytotoxic hemozoin (Hz) residues from digested hemoglobin (Hb) significantly contribute to this impairment of erythropoiesis. Here, we show that not only isolated Hz, but also delipidated Hz, produces a substantial inhibition of erythroid development in vitro, in the absence of TNF-. However, when added to cultures, TNF- synergizes with Hz to inhibit erythropoiesis. Furthermore, we show that, in children with malarial anemia, the proportion of circulating monocytes containing Hz is associated with anemia (P<0.001) and reticulocyte suppression (P=0.009), and that this is independent of the level of circulating cytokines, including TNF-. Plasma Hz is also associated with anemia (P<0.001) and reticulocyte suppression (P=0.02). Finally, histological examination of the bone marrow of children who have died from malaria, shows that pigmented erythroid and myeloid precursors are associated with the degree of abnormal erythroid development. Taken together these observations provide compelling evidence for inhibition of erythropoiesis by Hz. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. W. Griffith, T. Sun, M. T. McIntosh, and R. Bucala Pure Hemozoin Is Inflammatory In Vivo and Activates the NALP3 Inflammasome via Release of Uric Acid J. Immunol., October 15, 2009; 183(8): 5208 - 5220. [Abstract] [Full Text] [PDF] C. C. Keller, C. Ouma, Y. Ouma, G. A. Awandare, G. C. Davenport, T. Were, J. B. Hittner, J. M. Vulule, J. M. Ong'echa, and D. J. Perkins Suppression of a Novel Hematopoietic Mediator in Children with Severe Malarial Anemia Infect. Immun., September 1, 2009; 77(9): 3864 - 3871. [Abstract] [Full Text] [PDF] A. A. M. Fernandes, L. J. de Moura Carvalho, G. M. Zanini, A. M. R. da Silva Ventura, J. M. Souza, P. M. Cotias, I. L. Silva-Filho, and C. T. Daniel-Ribeiro Similar Cytokine Responses and Degrees of Anemia in Patients with Plasmodium falciparum and Plasmodium vivax Infections in the Brazilian Amazon Region Clin. Vaccine Immunol., April 1, 2008; 15(4): 650 - 658. [Abstract] [Full Text] [PDF] C. Casals-Pascual, R. Idro, N. Gicheru, S. Gwer, B. Kitsao, E. Gitau, R. Mwakesi, D. J. Roberts, and C. R. J. C. Newton High levels of erythropoietin are associated with protection against neurological sequelae in African children with cerebral malaria PNAS, February 19, 2008; 105(7): 2634 - 2639. [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] P. E. Brentlinger, C. B. Behrens, and J. G. Kublin Challenges in the Prevention, Diagnosis, and Treatment of Malaria in Human Immunodeficiency Virus Infected Adults in Sub-Saharan Africa Arch Intern Med, September 24, 2007; 167(17): 1827 - 1836. [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] G. A. Awandare, Y. Ouma, C. Ouma, T. Were, R. Otieno, C. C. Keller, G. C. Davenport, J. B. Hittner, J. Vulule, R. Ferrell, et al. Role of Monocyte-Acquired Hemozoin in Suppression of Macrophage Migration Inhibitory Factor in Children with Severe Malarial Anemia Infect. Immun., January 1, 2007; 75(1): 201 - 210. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020