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Terminal Maturation of Orthochromatic Erythroblasts Is Impaired in Burn Patients.

Journal of burn care & research : official publication of the American Burn Association (2017-06-02)
Shirin Hasan, Michael J Mosier, Peggie Conrad, Andrea Szilagyi, Richard L Gamelli, Kuzhali Muthumalaiappan
ABSTRACT

Mechanisms of erythropoietin (Epo)-resistant anemia in burn patients are poorly understood. We have recently found that administering a nonselective beta 1,2-adrenergic blocker propranolol (PR) was effective in reversing myelo-erythroid commitment through MafB regulation and increase megakaryocyte erythrocyte progenitors in burn patients' peripheral blood mononuclear cell (PBMC)-derived ex vivo culture system. Having known that Epo-dependent proliferation of early erythroblasts is intact after burn injury, here we inquired whether or not Epo-independent maturation stage of erythropoiesis is affected by burn injury and the relative role of PR on late-stage erythropoiesis. While majority of erythropoiesis occurs in the bone marrow, maturation into reticulocytes is crucial for their release into sinusoids to occupy the peripheral circulation for which enucleation is vital. peripheral blood mononuclear cells (PBMCs) from burn patients were extended beyond commitment and proliferation stages to late maturation stage in ex vivo culture to understand the role of PR in burn patients. Burn impedes late maturation of orthochromatic erythroblasts into reticulocytes by restricting the enucleation step. Late-stage erythropoiesis is impaired in burn patients irrespective of PR treatment. Further, substituting the microenvironment with control plasma (homologous) in place of autologous plasma rescues the conversion of orthochromatic erythroblasts to reticulocytes. Results show promise in formulating interventions to regulate late-stage erythropoiesis, which can be used in combination with PR to reduce the number of transfusions.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Giemsa stain, modified
Sigma-Aldrich
EPO human, recombinant, expressed in HEK 293 cells, ≥95% (SDS-PAGE)
Sigma-Aldrich
May-Grünwald Stain