Mediators of Prolonged Hematopoietic Progenitor Cell Mobilization After Severe Trauma

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. (c) 2020 Elsevier Inc. All rights reserved.

Automated summary

This study showed that propranolol could reduce the expression of HMGB1, G-CSF, and neutrophil elastase, resulting in a decreased mobilization of hematopoietic progenitor cells in response to chronic stress and trauma.