Hematopoietic progenitor cell mobilization is mediated through beta-2 and beta-3 receptors after injury.
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.
Beiermeister
Keith A
KA
Division of Trauma, Department of Surgery, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA.
Keck
Brett M
BM
Sifri
Ziad C
ZC
ElHassan
Ihab O
IO
Hannoush
Edward J
EJ
Alzate
Walter D
WD
Rameshwar
Pranela
P
Livingston
David H
DH
Mohr
Alicia M
AM
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
D000319:Adrenergic beta-Antagonists; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3