Abstract 402: Plasminogen Inhibits Sdf-1-induced Cxcr4 Internalization In Bone Marrow-derived Mononuclear Cells

Abstract

In multiple pathological settings including stokes and myocardial infarction (MI), stem cells are mobilized from the bone marrow to injury site to promote tissue repair. However, naturally recruited stem cells are not sufficient for heart function recovery. How to enhance stem cell mobilization remains challenge but may lead to develop novel strategy for stem cell therapies. Our previous studies have shown that Plasminogen (Plg) enhances stem cell mobilization and contributes to cardiac repair after MI. Mechanism studies reveal that Plg regulates CXCR4 expression, the receptor of SDF-1, a major chemoattractant for stem cells, during stem cell mobilization. Using bone marrow mononuclear cells, our data show that Plg is able to increase CXCR4 expression in a dose-dependent manner. Moreover, Plg decreases CXCR4 internalization induced by SDF-1. SDF-1 (50nM) induces a rapid internalization of CXCR4 on BMNC indicated as much lower CXCR4 expression compared with control (0.9 ± 0.5% vs 10.5 ± 2.6%) in cell surface. However, Plg treatment (100nM) decreases CXCR4 internalization, indicated as significantly higher expression (5.5 ± 0.9%) of CXCR4 on the cell surface. Immunofluorescent staining results show that CXCR4 translocates into cytoplasma after SDF-1 treatment. Plg rescued the CXCR4 translocation induced by SDF-1 and CXCR4 is mainly expressed on the cell surface as shown in the figure, confirming that Plg may prolong CXCR4 expression through inhibiting CXCR4 internalization by SDF-1. These data has indicated a novel mechanism for Plg-regulated CXCR4 expression and may contribute stem cell mobilization from bone marrow to the circulation during MI injury.