Abstract 3684: Reduced Expression of Adhesion Receptors CXCR4, LFA-1 and VLA-4 on G-CSF-mobilized CD34+ Progenitor Cells in Acute Myocardial Infarction
Introduction: G-CSF induced mobilization of progenitor cells is multistep processes involving chemokines, growth factors, matrix-degrading enzymes, and cell adhesive interactions mediated by specific receptors on hematopoietic cells. Members of the integrin family of adhesion receptors are widely expressed in the hematopoietic system, and both adhesion molecules “very late antigen 4” (VLA-4), “leukocyte function-associated antigen-1” (LFA-1) and “vascular cell adhesion molecule 1” (VCAM-1) as well as “stroma-cell derived factor-1” (SDF-1) and its receptor CXCR-4 play an important role in progenitor cell mobilization and homing.
Methods and Results: In the randomized, double-blind, placebo-controlled REVIVAL-2 study 114 patients with acute myocardial infarction were included. Five days after successful PCI patients received either 10 μg/kg G-CSF (n=56) or Placebo (n=58) subcutaneously for 5 days. Venous blood samples were analyzed on day 5 after therapy and progenitor cell mobilization and surface expression of VLA-4, LFA-1 and CXCR-4 were measured on circulating CD34+ cells using flow cytometry. G-CSF induced a significant increase in circulating CD34+ cells (72±20 cells/μl versus 4.5±0.8 cells/μl, P<0.05). Surface expression of LFA-1, VLA-4 and CXCR4 on CD34+ cells was decreased by 44%, 49% und 60% after G-CSF as compared to placebo (p<0.05). Moreover, levels of circulating soluble VCAM significantly increased and plasma SDF-1 concentrations decreased after therapy with G-CSF.
Conclusion: Decreased expression of adhesion and chemokine receptors on G-CSF mobilized CD34+ progenitor cells in acute myocardial infarction may alter the homing capacity of the circulating cells to the myocardium.