Hematopoietic Progenitor Cell Mobilization Is Mediated Through β-2 and β-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 β-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). β-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.

Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via β-adrenergic induction of myelopoiesis

“…Neural and endocrine dynamics could also conceivably expand the total body pool of monocytes via increased hematopoietic output of myeloid lineage immune cells (myelopoiesis) (23). Hematopoiesis and monocyte differentiation occur in a bone marrow microenvironment that receives direct innervation from the sympathetic nervous system (SNS) (24), and SNS activation can alter hematopoietic stem cell mobilization (25)(26)(27) and myelopoietic responses to systemic infection (28,29). It is not known whether social processes can influence monocyte differentiation, or what role the SNS might play in such dynamics.…”

Beta-Blockade Prevents Hematopoietic Progenitor Cell Suppression after Hemorrhagic Shock

“…In a subsequent study, a team from the same laboratory [20] found that the protection is mediated by beta-2 and beta-3 receptors; the beta-1 receptor had no impact on BM HPC growth [20]. In this study, using an HS model, we demonstrated similarly that the BM is protected via non-selective BB administration either before or immediately after HS.…”

β-Adrenergic receptor inhibition affects cerebral glucose metabolism, motor performance, and inflammatory response after traumatic brain injury

“…In a lung contusion model, A2 and A3 inhibition, as opposed to A1 inhibition, reduced both bone marrow suppression and hematopoietic precursor cell sequestration. 35 In a laparotomy model, cerebral immunologic changes were under BAR control, and not >-adrenergic receptor control, and BAR inhibition reduced proinflammatory cytokines. 36 BAR inhibition has also been studied in TBI models that we previously demonstrated with PET imaging and immunohistochemistry increased perfusion and reduced hypoxia with nonselective BAR inhibition.…”