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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Role of monocyte-acquired hemozoin in suppression of macrophage migration inhibitory factor in children with severe malarial anemia
Infection and Immunity, Volume 75, No. 1, Year 2007
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Description
Severe malarial anemia (SMA), caused by Plasmodium falciparum infections, is one of the leading causes of childhood mortality in sub-Saharan Africa. Although the molecular determinants of SMA are largely undefined, dysregulation in host-derived inflammatory mediators influences disease severity. Macrophage migration inhibitory factor (MIF) is an important regulator of innate inflammatory responses that has recently been shown to suppress erythropoiesis and promote pathogenesis of SMA in murine models. To examine the role of MIF in the development of childhood SMA, peripheral blood MIF production was examined in Kenyan children (aged <3 years, n = 357) with P. falciparum malarial anemia. All children in the study were free from bacteremia and human immunodeficiency virus type 1. Since deposition of malarial pigment (hemozoin [Hz]) contributes to suppression of erythropoiesis, the relationship between MIF concentrations and monocytic acquisition of Hz was also examined in vivo and in vitro. Circulating MIF concentrations declined with increasing severity of anemia and significantly correlated with peripheral blood leukocyte MIF transcripts. However, MIF concentrations in peripheral blood were not significantly associated with reticulocyte production. Multivariate regression analyses, controlling for age, gender, and parasitemia, further revealed that elevated levels of pigment-containing monocytes (PCM) was associated with SMA and decreased MIF production. In addition, PCM levels were a better predictor of hemoglobin and MIF concentrations than parasite density. Additional experiments in malaria-naive individuals demonstrated that hemozoin caused both increased and decreased MIF production in cultured peripheral blood mononuclear cells (PBMC) in a donor-specific manner, independent of apoptosis. However, PBMC MIF production in children with acute malaria progressively declined with increasing anemia severity. Results presented here demonstrate that acquisition of hemozoin by monocytes is associated with suppression of peripheral blood MIF production and enhanced severity of anemia in childhood malaria. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Awandare, Gordon Akanzuwine
United States, Pittsburgh
University of Pittsburgh Graduate School of Public Health
United States, Pittsburgh
University of Pittsburgh
Ghana, Accra
University of Ghana
Ouma, Yamo
United States, Pittsburgh
University of Pittsburgh
Ouma, Collins
United States, Pittsburgh
University of Pittsburgh
Were, Tom
United States, Pittsburgh
University of Pittsburgh
Otieno, Richard O.
United States, Pittsburgh
University of Pittsburgh
Keller, Christopher C.
United States, Erie
Lake Erie College of Osteopathic Medicine
Davenport, Gregory C.
United States, Pittsburgh
University of Pittsburgh Graduate School of Public Health
Hittner, James Bryant
United States, Charleston
College of Charleston
Vulule, John M.
Kenya, Nairobi
Kenya Medical Research Institute
Ferrell, Robert E.
United States, Pittsburgh
University of Pittsburgh Graduate School of Public Health
Ong'Echa, John Michael O.
United States, Pittsburgh
University of Pittsburgh
Perkins, Douglas Jay
United States, Pittsburgh
University of Pittsburgh Graduate School of Public Health
United States, Pittsburgh
University of Pittsburgh
Statistics
Citations: 90
Authors: 12
Affiliations: 6
Identifiers
Doi:
10.1128/IAI.01327-06
ISSN:
00199567
Research Areas
Cancer
Infectious Diseases
Maternal And Child Health