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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Suppression of erythropoiesis in malarial anemia is associated with hemozoin in vitro and in vivo
Blood, Volume 108, No. 8, Year 2006
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Description
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-α (TNF-α), 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-α. However, when added to cultures, TNF-α 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 < .001) and reticulocyte suppression (P = .009), and that this is independent of the level of circulating cytokines, including TNF-α. 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. © 2006 by The American Society of Hematology.
Authors & Co-Authors
Casals-Pascual, Climent
United Kingdom, Bristol
Nhs Blood and Transplant
Kai, Oscar K.
Unknown Affiliation
Lowe, Brett S.
Unknown Affiliation
Nyanoti, Mike
Unknown Affiliation
Williams, Thomas Neil
Unknown Affiliation
Maitland, Kathryn M.
Unknown Affiliation
Molyneux, Malcolm Edward
Unknown Affiliation
Newton, Charles R.J.C.
Unknown Affiliation
Peshu, Norbert M.
Unknown Affiliation
Roberts, David J.
Unknown Affiliation
Statistics
Citations: 181
Authors: 10
Affiliations: 1
Identifiers
Doi:
10.1182/blood-2006-05-018697
ISSN:
00064971
Research Areas
Cancer
Infectious Diseases
Maternal And Child Health