Expression of CXCR4, VLA-1, LFA-3 and transducer of ERB in G-CSF-mobilised progenitor cells in acute myocardial infarction

Thromb Haemost. 2010 Mar;103(3):638-43. doi: 10.1160/TH09-09-0657. Epub 2010 Jan 13.

Abstract

G-CSF induced mobilisation of progenitor cells is a multistep processes involving chemokines, growth factors, matrix-degrading enzymes, and cell adhesive interactions mediated by specific receptors on haematopoietic cells. This study's aim was to investigate progenitor cells mobilised during myocardial infarction after treatment with granulocyte-stimulating factor (G-CSF). In the randomised, double-blind, placebo-controlled REVIVAL-2 study, 114 patients with acute myocardial infarction were included. Five days after successful percutaneous coronary intervention patients received either 10 microg/kg G-CSF (n=56) or placebo (n=58) subcutaneously for five days. Venous blood samples were analysed on day(s) 1, 3, 5 and 7 after therapy, and progenitor cell mobilisation and surface expression of VLA-4, LFA-1 and CXCR-4 was measured on circulating progenitor cells using flow cytometry. G-CSF induced a significant increase in circulating progenitor cells (72 +/- 20 cells/microl vs. 4.5 +/- 0.8 cells/microl, p<0.05). Surface expression of LFA-1, VLA-4 and CXCR4 on progenitor cells was decreased by 44%, 49% and 60% after G-CSF as compared to placebo (p<0.05). In accordance, mRNA expression of CXCR4 was reduced. Moreover, anti-proliferative transducer of ERB (TOB) mRNA was decreased, suggesting an increased proliferative potential of the mobilised progenitor cells. Decreased expression of adhesion and chemokine receptors on G-CSF mobilised progenitor cells in acute myocardial infarction may alter the homing capacity of circulating cells to the myocardium.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD58 Antigens / analysis
  • Double-Blind Method
  • Flow Cytometry
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Hematopoietic Stem Cell Mobilization / methods
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Integrin alpha1beta1 / analysis
  • Intracellular Signaling Peptides and Proteins / analysis*
  • Myocardial Infarction / drug therapy*
  • Receptors, CXCR4 / analysis
  • Receptors, Cell Surface / analysis
  • Receptors, Cell Surface / drug effects*
  • Tumor Suppressor Proteins / analysis*

Substances

  • CD58 Antigens
  • Integrin alpha1beta1
  • Intracellular Signaling Peptides and Proteins
  • Receptors, CXCR4
  • Receptors, Cell Surface
  • TOB1 protein, human
  • Tumor Suppressor Proteins
  • Granulocyte Colony-Stimulating Factor