Modulation of the HGF/c-Met Axis Impacts Prolonged Hematopoietic Progenitor Mobilization Following Trauma and Chronic Stress

• Published in: Shock (Augusta, Ga.) Ga.), 2020-10, Vol.54 (4), p.482-487
• Main Authors: Loftus, Tyler J., Kannan, Kolenkode B., Mira, Juan C., Brakenridge, Scott C., Efron, Philip A., Mohr, Alicia M.
• Format: Article
• Language: English
• ISSN: 1073-2322; 1540-0514
• DOI: 10.1097/SHK.0000000000001506

BACKGROUND:Trauma and hemorrhagic shock trigger mobilization of hematopoietic progenitor cells (HPC) from bone marrow to peripheral blood. Hepatocyte growth factor (HGF), tyrosine-protein kinase Met (c-Met), matrix metallopeptidase 9 (MMP-9), and corticosterone regulate this mobilization process. We hypothesized that beta-blockade with propranolol and sympathetic outflow inhibition with clonidine following trauma and chronic stress would decrease hematopoietic progenitor cell mobilization. METHODS:Sprague-Dawley rats were randomized to undergo three models of injury and stresslung contusion, LC plus hemorrhagic shock (LCHS), or LCHS plus chronic restraint stress for 2 h daily (LCHS/CS). Propranolol and clonidine were administered by daily intraperitoneal injection until sacrifice on day seven. Bone marrow HGF, c-Met, and MMP-9 were measured by real-time PCR. Plasma corticosterone was measured by ELISA. Percentage HPC in peripheral blood was measured by flow cytometry. RESULTS:Propranolol and clonidine significantly decreased bone marrow MMP-9 expression, plasma corticosterone levels, and HPC mobilization, and significantly increased hemoglobin levels. HPC mobilization was greatest following LCHS/CS (5.4 ± 1.8) and was significantly decreased by propranolol (2.2 ± 0.9, P