Deutsches Herzzentrum und 1. Medizinische Klinik der Technischen Universität München, Germany.
Thromb Haemost. 2010 Mar;103(3):638-43. doi: 10.1160/TH09-09-0657. Epub 2010 Jan 13.
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.
G-CSF 诱导祖细胞动员是一个多步骤的过程,涉及趋化因子、生长因子、基质降解酶,以及造血细胞上特定受体介导的细胞黏附相互作用。本研究旨在探讨粒细胞集落刺激因子(G-CSF)治疗急性心肌梗死后动员的祖细胞。在随机、双盲、安慰剂对照的 REVIVAL-2 研究中,纳入了 114 例急性心肌梗死患者。经皮冠状动脉介入治疗成功后第 5 天,患者接受皮下注射 10 μg/kg G-CSF(n=56)或安慰剂(n=58),连续 5 天。在治疗后第 1、3、5 和 7 天采集静脉血样本,并使用流式细胞术检测循环祖细胞中祖细胞动员和 VLA-4、LFA-1 和 CXCR-4 的表面表达。G-CSF 诱导循环祖细胞显著增加(72±20 个/μl 比 4.5±0.8 个/μl,p<0.05)。与安慰剂相比,G-CSF 后祖细胞上的 LFA-1、VLA-4 和 CXCR4 表面表达分别下降 44%、49%和 60%(p<0.05)。相应地,CXCR4 的 mRNA 表达减少。此外,ERB(TOB)mRNA 的增殖转录因子减少,提示动员的祖细胞增殖潜力增加。急性心肌梗死后 G-CSF 动员的祖细胞上黏附分子和趋化因子受体表达降低,可能改变循环细胞归巢到心肌的能力。