Burn Injury Dampens Erythroid Cell Production Through Reprioritizing Bone Marrow Hematopoietic Response

• Published in: The Journal of trauma, injury, infection, and critical care Vol. 71; no. 5; pp. 1288 - 1296
• Main Authors: Posluszny, Joseph A., Muthumalaiappan, Kuzhali, Kini, Ameet R., Szilagyi, Andrea, He, Li-Ke, Li, Yanxia, Gamelli, Richard L., Shankar, Ravi
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins, Inc 01-11-2011; Lippincott Williams & Wilkins
• Subjects: Analysis of Variance; Anemia - etiology; Anemia - metabolism; Animals; Biological and medical sciences; Bone Marrow Cells - metabolism; Burns; Burns - complications; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Diseases of the osteoarticular system; Erythroid Cells - metabolism; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Hematopoietic System - metabolism; Lymphocytes - metabolism; Male; Medical sciences; Mice; Molecular and cellular biology; Myeloid Cells - metabolism; Random Allocation; Reticulocytes - metabolism; Traumas. Diseases due to physical agents; Burn; Erythropoiesis; Erythropoietin; Polypeptide; Hematopoiesis; Production; Bone marrow; Anesthesia; Bone marrow response; Burn injury
• ISSN: 0022-5282; 1529-8809
• DOI: 10.1097/TA.0b013e31822e2803

BACKGROUND:Anemia in burn patients is due to surgical blood loss and anemia of critical illness. Because the commitment paradigm of common bone marrow progenitors dictates the production of erythroid, myeloid, and lymphoid cells, we hypothesized that skewed bone marrow lineage commitment decreases red cell production and causes anemia after a burn injury.
METHODS:After anesthesia, B6D2F1 mice received a 15% total body surface area dorsal scald burn. The sham group did not receive scald burn. Femoral bone marrow was harvested on 2, 5, 7, 14, and 21 postburn days (PBD). Total bone marrow cells were labeled with specific antibodies to erythroid (CD71/Ter119), myeloid (CD11b), and lymphoid (CD19) lineages and analyzed by flow cytometry. To test whether erythropoietin (EPO) could increase red blood cell production, EPO was administered to sham and burn animals and their reticulocyte response was measured on PBD 2 and PBD 7.
RESULTS:Burn injury reduced the erythroid cells of the bone marrow from 35% in sham to 17% by PBD 5 and remained at similar level until PBD 21. Myeloid cells, however, increased from 42% in sham to 60% on PBD 5 and 77% on PBD 21. Burn injury reduced reticulocyte counts on PBD 2 and PBD 7 indicating that the erythroid compartment is severely depleted. This depleted compartment, however, responded to EPO but was not sufficient to change red cell production.
CONCLUSION:Burn injury skews the bone marrow hematopoietic commitment away from erythroid and toward myeloid cells. Shrinkage of the erythroid compartment contributes to resistance to EPO and the anemia of critical illness.