title: β-blockade protection of bone marrow following trauma: the role of G-CSF.
abstract: BACKGROUND
  Following severe trauma, there is a profound elevation of catecholamine that is associated with a persistent anemic state. We have previously shown that β-blockade (βB) prevents erythroid growth suppression and decreases hematopoietic progenitor cell (HPC) mobilization following injury. Under normal conditions, granulocyte colony stimulating factor (G-CSF) triggers the activation of matrix metalloprotease-9 (MMP-9), leading to the egress of progenitor cells from the bone marrow (BM). When sustained, this depletion of BM cellularity may contribute to BM failure. This study seeks to determine if G-CSF plays a role in the βB protection of BM following trauma.
  
  
  METHODS
  Male Sprague-Dawley rats were subjected to either unilateral lung contusion (LC) ± βB, hemorrhagic shock (HS) ± βB, or both LC/HS ± βB. Propranolol (βB) was given immediately following resuscitation. Animals were sacrificed at 3 and 24 h and HPC mobilization was assessed by evaluating BM cellularity and flow cytometric analysis of peripheral blood for HPCs. The concentration of G-CSF and MMP-9 was measured in plasma by ELISA.
  
  
  RESULTS
  BM cellularity is decreased at 3 h following LC, HS, and LC/HS. HS and LC/HS resulted in significant HPC mobilization in the peripheral blood. The addition of βB restored BM cellularity and reduced HPC mobilization. Three h following HS and LC/HS, plasma G-CSF levels more than double, however LC alone showed no change in G-CSF. βB significantly decreased G-CSF in both HS and LC/HS. Similarly, MMP-9 is elevated following LC/HS, and βB prevents this elevation (390 ± 100 pg/mL versus 275 ± 80 pg/mL).
  
  
  CONCLUSIONS
  βB protection of the BM following shock and injury may be due to reduced HPC mobilization and maintenance of BM cellularity. Following shock, there is an increase in plasma G-CSF and MMP-9, which is abrogated by βB and suggests a possible mechanism how βB decreases HPC mobilization thus preserving BM cellularity. In contrast, βB protection of BM following LC is not mediated by G-CSF. Therefore, the mechanism of progenitor cell mobilization from the BM is dependent on the type of injury.
authors.affiliation: Department of Surgery, Division of Trauma, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School, Newark, New Jersey 07103, USA.
authors.forename: Gregg M
authors.initials: GM
authors.lastname: Baranski
authors.forename: Michael D
authors.initials: MD
authors.lastname: Offin
authors.forename: Ziad C
authors.initials: ZC
authors.lastname: Sifri
authors.forename: Ihab O
authors.initials: IO
authors.lastname: Elhassan
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Hannoush
authors.forename: Walter D
authors.initials: WD
authors.lastname: Alzate
authors.forename: Pranela
authors.initials: P
authors.lastname: Rameshwar
authors.forename: David H
authors.initials: DH
authors.lastname: Livingston
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Mohr
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism; D003288:Contusions / Q000150:complications; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000502:physiology*; D019650:Hematopoietic Stem Cell Mobilization; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications; D014947:Wounds and Injuries / Q000150:complications*
chemical_list: D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D016179:Granulocyte Colony-Stimulating Factor; D011433:Propranolol; D020780:Matrix Metalloproteinase 9