Myelo-erythroid commitment after burn injury is under beta-adrenergic control via MafB regulation Journal Article

Authors: Hasan, S.; Johnson, N. B.; Mosier, M. J.; Shankar, R.; Conrad, P.; Szilagyi, A.; Gamelli, R. L.; Muthumalaiappan, K.
Article Title: Myelo-erythroid commitment after burn injury is under beta-adrenergic control via MafB regulation
Abstract: Severely injured burn patients receive multiple blood transfusions for anemia of critical illness despite the adverse consequences. One limiting factor to consider alternate treatment strategies is the lack of a reliable test platform to study molecular mechanisms of impaired erythropoiesis. This study illustrates how conditions resulting in a high catecholamine microenvironment such as burns can instigate myelo-erythroid reprioritization influenced by beta-adrenergic stimulation leading to anemia. In a mouse model of scald burn injury, we observed, along with a threefold increase in bone marrow LSK cells (linneg Sca1+cKit+), that the myeloid shift is accompanied with a significant reduction in megakaryocyte erythrocyte progenitors (MEPs). beta-Blocker administration (propranolol) for 6 days after burn, not only reduced the number of LSKs and MafB+ cells in multipotent progenitors, but also influenced myelo-erythroid bifurcation by increasing the MEPs and reducing the granulocyte monocyte progenitors in the bone marrow of burn mice. Furthermore, similar results were observed in burn patients' peripheral blood mononuclear cell-derived ex vivo culture system, demonstrating that commitment stage of erythropoiesis is impaired in burn patients and intervention with propranolol (nonselective beta1,2-adrenergic blocker) increases MEPs. Also, MafB+ cells that were significantly increased following standard burn care could be mitigated when propranolol was administered to burn patients, establishing the mechanistic regulation of erythroid commitment by myeloid regulatory transcription factor MafB. Overall, results demonstrate that beta-adrenergic blockers following burn injury can redirect the hematopoietic commitment toward erythroid lineage by lowering MafB expression in multipotent progenitors and be of potential therapeutic value to increase erythropoietin responsiveness in burn patients.
Keywords: Burns; Anemia; propranolol; LSK cells; MafB; catecholamine; erythro-myeloid; erythropoiesis; granulocyte monocyte progenitors; megakaryocyte erythrocyte progenitors
Journal Title: American journal of physiology.Cell physiology
Volume: 312
Issue: 3
ISSN: 1522-1563; 0363-6143
Publisher: the American Physiological Society  
Journal Place: United States
Date Published: 2017
Start Page: C286
End Page: C301
Language: eng
Notes: LR: 20170311; CI: Copyright (c) 2017; GR: R01 DK097760/DK/NIDDK NIH HHS/United States; JID: 100901225; OTO: NOTNLM; 2016/05/17 [received]; 2016/12/22 [revised]; 2016/12/22 [accepted]; ppublish