Expression of CXCR4, VLA-1, LFA-3 and transducer of ERB in G-CSF-mobilised progenitor cells in acute myocardial infarction.
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.
Stein
Andreas
A
Deutsches Herzzentrum und 1. Medizinische Klinik der Technischen Universität München, Germany.
Zohlnhöfer
Dietlind
D
Pogatsa-Murray
Gisela
G
von Wedel
Jasper
J
Steppich
Birgit A
BA
Schömig
Albert
A
Kastrati
Adnan
A
Ott
Ilka
I
D018968:CD58 Antigens / Q000032:analysis; D004311:Double-Blind Method; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D039222:Integrin alpha1beta1 / Q000032:analysis; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis*; D009203:Myocardial Infarction / Q000188:drug therapy*; D019718:Receptors, CXCR4 / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis / Q000187:drug effects*; D025521:Tumor Suppressor Proteins / Q000032:analysis*
D018968:CD58 Antigens; D039222:Integrin alpha1beta1; D047908:Intracellular Signaling Peptides and Proteins; D019718:Receptors, CXCR4; D011956:Receptors, Cell Surface; C098669:TOB1 protein, human; D025521:Tumor Suppressor Proteins; D016179:Granulocyte Colony-Stimulating Factor