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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3727-3735.
Prepublished online as a Blood First Edition Paper on January 22, 2004; DOI 10.1182/blood-2003-08-2887.
Submitted August 22, 2003
Accepted January 8, 2004
Inappropriately Low Reticulocytosis in Severe Malarial Anemia Correlates with Suppression in the Development of Late Erythroid Precursors
Kai-Hsin Chang, Mifong Tam, and Mary M Stevenson*
Institute of Parasitology, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada; Department of Medicine, McGill University, Montreal, Quebec, Canada
Department of Medicine, McGill University, Montreal, Quebec, Canada
* Corresponding author; email: mary.m.stevenson{at}mcgill.ca.
Inappropriately low reticulocytosis may exacerbate malarial anemia but the underlying mechanism is not clear. In this study, naive and infected mice were treated with recombinant murine erythropoietin (EPO) and the up-stream events of erythropoiesis affected by blood-stage Plasmodium chabaudi AS were investigated. Malaria infection, with or without EPO treatment, led to a sub-optimal increase in TER119+ erythroblasts compared to EPO-treated naive mice. Furthermore, a lower percentage of TER119+ erythroblasts in infected mice was undergoing terminal differentiation to become mature hemoglobin-producing erythroblasts. The impaired maturation of erythroblasts during infection was associated with a shift in the transferrin receptor (CD71) expression from the TER119+ population to B220+ population. Moreover, the sub-optimal increase in TER119+ erythroblasts during infection coincided with a blunted proliferative response by splenocytes to EPO stimulation in vitro although a high frequency of these splenocytes expressed EPO receptor (EPOR). Taken together, these data suggest that during malaria, EPO-induced proliferation of early EPOR+ erythroid progenitors is suppressed, which may lead to a sub-optimal generation of TER119+ erythroblasts. The shift in CD71 expression may result in impaired terminal maturation of these erythroblasts. Thus, inadequate reticulocytosis during malaria is associated with suppressed proliferation, differentiation, and maturation of erythroid precursors.
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