Mediators of Prolonged Hematopoietic Progenitor Cell Mobilization After Severe Trauma.

Abstract

BACKGROUND:

This study investigated the molecular mediators of prolonged hematopoietic progenitor cell mobilization a trauma and chronic stress and the role of propranolol in modifying this response.

METHODS:

Sprague-Dawley rats were randomized to lung contusion (LC), LC plus hemorrhagic shock (LCHS), or LCHS with daily restraint stress (LCHS/CS). Propranolol was administered daily. Bone marrow (BM) and lung expression of high mobility group box 1 (HMGB1), granulocyte colony-stimulating factor (G-CSF), neutrophil elastase, stromal cell-derived factor 1 (SDF-1)/CXR4, and vascular cell adhesion protein 1 (VCAM-1)/very late antigen-4 were measured by real-time polymerase chain reaction.

RESULTS:

Bone marrow HMGB1, G-CSF, and neutrophil elastase expression were significantly elevated two- to four-fold after LCHS/CS, and all were decreased with the use of propranolol. SDF-1 and VCAM-1 were both significantly decreased after LCHS/CS.

CONCLUSIONS:

The increased expression of HMGB1 and G-CSF and decreased expression of BM anchoring molecules, SDF-1 and VCAM-1, after LCHS/CS, likely mediates prolonged hematopoietic progenitor cell mobilization. Propranolol's ability to reduce HMGB1, G-CSF, and neutrophil elastase expression suggests that the mobilization of hematopoietic progenitor cells was driven by persistent hypercatecholaminemia.

• Authors: Getasha D Doobay, Elizabeth S Miller, Camille G Apple, Tyler J Loftus, Kolenkode B Kannan, Philip A Efron, Alicia M Mohr
• Journal: The Journal of surgical research (J Surg Res) Vol. 260 Pg. 315-324 (04 2021) ISSN: 1095-8673 [Electronic] United States
• PMID: 33373851 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Adrenergic beta-Antagonists
• Biomarkers
• Propranolol

Topics

• Adrenergic beta-Antagonists (pharmacology, therapeutic use)
• Animals
• Biomarkers (metabolism)
• Bone Marrow (drug effects, metabolism)
• Chronic Disease
• Contusions (drug therapy, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Hematopoietic Stem Cells (drug effects, metabolism)
• Lung Injury (drug therapy, metabolism)
• Male
• Propranolol (pharmacology, therapeutic use)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Restraint, Physical
• Shock, Hemorrhagic (drug therapy, metabolism)
• Stress, Physiological (physiology)