title: Hematopoietic progenitor cell mobilization is mediated through beta-2 and beta-3 receptors after injury.
abstract: BACKGROUND
  Hematopoietic progenitor cells (HPCs) are mobilized into the peripheral blood (PB) and then sequestered in injured tissue after trauma. Nonselective beta-adrenergic blockade (BB) has been shown to cause a decrease in mobilization of HPCs to the periphery and to injured tissue. Given the vast physiologic effects of nonselective BB, the aim of this study is to delineate the role of selective BB in HPC growth and mobilization.
  
  
  METHODS
  Rats underwent daily intraperitoneal injections of propranolol (Prop), atenolol (B1), butoxamine (B2), or SR59230A (B3) for 3 days to induce BB. All groups then underwent lung contusion (LC). HPC presence was assessed by GEMM, BFU-E, and CFU-E colony growth both in injured lung and bone marrow (BM). Flow cytometry, using c-kit and CD71, was used to determine mobilization into PB.
  
  
  RESULTS
  LC alone decreased BM HPC growth in all erythroid cell types and increased their number in injured lung (all *p < 0.05). beta-Blockade with Prop, B2, and B3 blockades restored BM HPC growth to control levels and decreased HPCs recovered in the injured lung. Similarly, Prop, B2, and B3 blockade prevented HPC mobilization to PB. B1 blockade with atenolol had no impact on HPC growth and mobilization following LC.
  
  
  CONCLUSIONS
  Nonselective BB reduced suppression of HPC growth in BM after injury and prevented the mobilization and subsequent sequestration of HPCs in injured tissue. Our data have shown that this effect is mediated through the B2 and B3 receptors. Therefore, after trauma, treatment with selective B2 or B3 blocker may attenuate the BM suppression associated with tissue injury.
authors.affiliation: Division of Trauma, Department of Surgery, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Beiermeister
authors.forename: Brett M
authors.initials: BM
authors.lastname: Keck
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*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D055370:Lung Injury / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3