Plasma TNFa and Unknown Factor/S Potentially Impede Erythroblast Enucleation Obstructing Terminal Maturation of Red Blood Cells in Burn Patients. Journal Article

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Authors: Walczak, J; Hasan, S; Shoaee, N; Tromblay, D; Muthumalaiappan, K
Article Title: Plasma TNFa and Unknown Factor/S Potentially Impede Erythroblast Enucleation Obstructing Terminal Maturation of Red Blood Cells in Burn Patients.
Abstract: INTRODUCTION: In this study, using burn patient's PBMCs, we have shown that the Epo independent stage of the terminal enucleation stage to reticulocyte formation is impeded in the presence of autologous plasma (BP). Furthermore, substitution with allogeneic control plasma (CP) from the healthy individual in place of BP rectified this enucleation defect. The exclusive role of burn microenvironment in late stage erythropoiesis defect was further demarcated through control healthy human bone marrow cells cultured in the presence of CP, BP and cytokines. METHODS: PBMCs and huBM were differentiated ex vivo to enucleated reticulocytes in the presence of required growth factors and 5% CP or BP. Effect of systemic mediators in burn microenvironment like IL-6, IL-15, and TNFa was also explored. Neutralization experiments were carried out by adding varying concentrations (25ng to 400ng/ml) of Anti-TNFa Ab to either CP+TNFa or BP. RESULTS: Reticulocyte proportion and maturation index were significantly improved upon substituting BP with CP during differentiation of burn PBMCs. In the huBM ex vivo culture, addition of IL-6 and IL-15 to CP inhibited the proliferation stages of erythropoiesis, whereas TNFa supplementation caused maximum diminution at erythroblast enucleation stage. Supplementation with anti-TNFa in the BP showed significant but partial restoration in the enucleation process, revealing the possibility of other crucial microenvironmental factors that could impact RBC production in burn patients. CONCLUSION: Exogenous TNFa impairs late-stage erythropoiesis by blocking enucleation, but neutralization of TNFa in BP only partially restored terminal enucleation indicating additional plasma factor(s) impair(s) late stage RBC maturation in burn patients.
Journal Title: Shock
ISSN: 1540-0514; 1073-2322
Publisher: Unknown  
Date Published: 2020