Summary
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 μg/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/μl vs. 4.5 ± 0.8 cells/μl, 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.
Keywords
G-CSF - progenitor cells - acute myocardial infarction - adhesion receptors