title: Inappropriately low reticulocytosis in severe malarial anemia correlates with suppression in the development of late erythroid precursors.
abstract: Inappropriately low reticulocytosis may exacerbate malarial anemia, but the under-lying mechanism is not clear. In this study, naive and infected mice were treated with recombinant murine erythropoietin (EPO), and the upstream events of erythropoiesis affected by blood-stage Plasmodium chabaudi AS were investigated. Malaria infection, with or without EPO treatment, led to a suboptimal increase in TER119(+) erythroblasts compared with EPO-treated naive mice. Furthermore, a lower percentage of TER119(+) erythroblasts in infected mice were 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 suboptimal 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-positive erythroid progenitors is suppressed, which may lead to a suboptimal 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.
authors.affiliation: Institute of Parasitology, McGill University, Ste-Anne-de-Bellevue, QC, Canada.
authors.forename: Kai-Hsin
authors.initials: KH
authors.lastname: Chang
authors.forename: Mifong
authors.initials: M
authors.lastname: Tam
authors.forename: Mary M
authors.initials: MM
authors.lastname: Stevenson
mesh_terms: D000740:Anemia / Q000209:etiology* / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D015672:Erythroid Precursor Cells / Q000469:parasitology* / Q000473:pathology; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use; D017493:Leukocyte Common Antigens / Q000032:analysis; D008288:Malaria / Q000150:complications* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016788:Plasmodium chabaudi; D011990:Receptors, Transferrin / Q000235:genetics; D011994:Recombinant Proteins; D045262:Reticulocytosis; D013154:Spleen / Q000378:metabolism / Q000469:parasitology / Q000473:pathology
chemical_list: D011990:Receptors, Transferrin; D011994:Recombinant Proteins; D004921:Erythropoietin; D017493:Leukocyte Common Antigens