title: Burn injury dampens erythroid cell production through reprioritizing bone marrow hematopoietic response.
abstract: 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, B(6)D(2)F(1) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Loyola University Medical Center, Burn and Shock Trauma Institute, Maywood, Illinois 60153, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Posluszny
authors.forename: Kuzhali
authors.initials: K
authors.lastname: Muthumalaiappan
authors.forename: Ameet R
authors.initials: AR
authors.lastname: Kini
authors.forename: Andrea
authors.initials: A
authors.lastname: Szilagyi
authors.forename: Li-Ke
authors.initials: LK
authors.lastname: He
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Li
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gamelli
authors.forename: Ravi
authors.initials: R
authors.lastname: Shankar
mesh_terms: D000704:Analysis of Variance; D000740:Anemia / Q000209:etiology* / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D002056:Burns / Q000150:complications*; D041905:Erythroid Cells / Q000378:metabolism*; D005434:Flow Cytometry; D006413:Hematopoietic System / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D022423:Myeloid Cells / Q000378:metabolism*; D011897:Random Allocation; D012156:Reticulocytes / Q000378:metabolism
references.citation: Ann Surg. 1973 Feb;177(2):139-43
references.pmid: 4144600
references.citation: J Trauma. 2007 Apr;62(4):858-67
references.pmid: 17426540
references.citation: Ann Surg. 2004 Jul;240(1):132-41
references.pmid: 15213629
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17413-8
references.pmid: 19805084
references.citation: Crit Care Med. 2006 Jun;34(6):1602-7
references.pmid: 16607231
references.citation: J Trauma. 1968 Nov;8(6):1049-51
references.pmid: 5722120
references.citation: J Trauma. 1981 Jan;21(1):13-21
references.pmid: 7463532
references.citation: Burns Incl Therm Inj. 1984 Apr;10(4):236-51
references.pmid: 6713238
references.citation: Expert Rev Mol Med. 2010 Feb 15;12:e6
references.pmid: 20152067
references.citation: Br J Haematol. 2000 May;109(2):280-7
references.pmid: 10848813
references.citation: J Trauma. 1982 Sep;22(9):774-80
references.pmid: 7120531
references.citation: J Clin Lab Anal. 2001;15(5):260-6
references.pmid: 11574955
references.citation: J Trauma. 2009 May;66(5):1273-80
references.pmid: 19430226
references.citation: J Cell Physiol. 1995 Jan;162(1):134-8
references.pmid: 7814445
references.citation: J Immunol. 1998 Apr 15;160(8):3861-8
references.pmid: 9558091
references.citation: J Trauma. 1995 Feb;38(2):233-6
references.pmid: 7869442
references.citation: Thromb Haemost. 2004 Aug;92(2):275-80
references.pmid: 15269822
references.citation: Proc Natl Acad Sci U S A. 1981 May;78(5):3039-43
references.pmid: 6265934
references.citation: J Burn Care Res. 2009 Jan-Feb;30(1):8-18
references.pmid: 19060758
references.citation: N Engl J Med. 2007 Sep 6;357(10):965-76
references.pmid: 17804841
references.citation: Blood. 1992 Aug 1;80(3):642-50
references.pmid: 1638021
references.citation: Ann Surg. 2001 Jan;233(1):97-106
references.pmid: 11141231
references.citation: J Trauma. 2011 Jul;71(1):26-31
references.pmid: 21131855
references.citation: J Burn Care Res. 2006 Nov-Dec;27(6):835-41
references.pmid: 17091079
references.citation: Burns Incl Therm Inj. 1985 Oct;12(1):22-7
references.pmid: 4063867
references.citation: Crit Care Med. 2009 Jun;37(6):1906-12
references.pmid: 19384207
references.citation: Surg Infect (Larchmt). 2004 Winter;5(4):385-93
references.pmid: 15744130
references.citation: Oncogene. 2002 May 13;21(21):3295-313
references.pmid: 12032771
references.citation: J Burn Care Res. 2008 Jan-Feb;29(1):12-21
references.pmid: 18182893