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Suppression of erythropoiesis in malarial anemia is associated with hemozoin in vitro and in vivo

Show simple item record Casals-Pascual, C. en_US Kai, O. en_US Cheung, J.O. en_US Williams, S. en_US Lowe, B. en_US Nyanoti, M. en_US Williams, T.N. en_US Maitland, K. en_US Molyneux, M. en_US Newton, C.R. en_US Peshu, N. en_US Watt, S.M. en_US Roberts, D.J. en_US 2014-10-29T09:24:10Z 2014-10-29T09:24:10Z 2006 en_US
dc.identifier.citation Blood. 2006; 108(8): pp.2569-2577 en_US
dc.identifier.issn 0006-4971 (Print) en_US
dc.identifier.issn 1528-0020 (Electronic) en_US
dc.description Indexed in MEDLINE
dc.description.abstract Malarial anemia is a global public health problem and is characterized by a low reticulocyte response in the presence of life-threatening hemolysis. Although cytokines, in particular tumor necrosis factor-alpha (TNF-alpha), can suppress erythropoiesis, the grossly abnormal bone marrow morphology indicates that other factors may contribute to ineffective erythropoiesis. We hypothesized that the cytotoxic hemozoin (Hz) residues from digested hemoglobin (Hb) significantly contribute to abnormal erythropoiesis. Here, we show that not only isolated Hz, but also delipidated Hz, inhibits erythroid development in vitro in the absence of TNF-alpha. However, when added to cultures, TNF-alpha synergizes with Hz to inhibiterythropoiesis. Furthermore, we show that, in children with malarial anemia, the proportion of circulating monocytes containing Hz is associated withanemia (P < .001) and reticulocyte suppression (P = .009), and that this is independent of the level of circulating cytokines, including TNF-alpha. Plasma Hz is also associated with anemia (P < .001) and reticulocyte suppression (P = .02). Finally, histologic 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.
dc.publisher American Society of Hematology en_US
dc.subject Malaria en_US
dc.subject Anemia-blood en_US
dc.subject Erythropoiesis-drug effects en_US
dc.subject Hemeproteins-toxicity en_US
dc.subject Malaria, Falciparum-blood en_US
dc.subject Malaria, Falciparum-complications en_US
dc.title Suppression of erythropoiesis in malarial anemia is associated with hemozoin in vitro and in vivo en_US
dc.type Article en_US
dc.identifier.department Pathology en_US
dc.creator.corporateauthor American Society of Hematology en_US

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