Burnham Ellen L, Taylor W Robert, Quyyumi Arshed A, Rojas Mauricio, Brigham Kenneth L, Moss Marc
Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Emory University School of Medicine, and the Atlanta Venterans' Affairs Medical Center, Atlanta, GA 30335, USA.
Am J Respir Crit Care Med. 2005 Oct 1;172(7):854-60. doi: 10.1164/rccm.200410-1325OC. Epub 2005 Jun 23.
Repair of damaged endothelium is important in recovery from acute lung injury. In animal models, bone marrow-derived endothelial progenitor cells differentiate into mature endothelium and assist in repairing damaged vasculature.
The quantity of endothelial progenitor cells in patients with acute lung injury is unknown. We hypothesize that increased numbers of circulating endothelial progenitor cells will be associated with an improved outcome in acute lung injury and the acute respiratory distress syndrome.
Peripheral blood mononuclear cells from the buffy coat of patients with early acute lung injury (n=45), intubated control subjects (n=10), and healthy volunteers (n=7) were isolated using Ficoll density gradient centrifugation, and plated on fibronectin-coated cellware. After 24 hours, nonadherent cells were removed and replated on fibronectin-coated cellware at a concentration of 1x10(6) cells/well. Colony-forming units were counted after 7 days' incubation.
MEASUREMENTS/MAIN RESULTS: Endothelial progenitor cell colony numbers were significantly higher in patients with acute lung injury compared with healthy control subjects (p<0.05), but did not differ between patients with acute lung injury and intubated control subjects. However, in the 45 patients with acute lung injury, improved survival correlated with a higher colony count (p<0.04). Patients with acute lung injury with a colony count of >or= 35 had a mortality of 30%, compared with 61% in those with colony counts <35 (p<0.03), results that persisted in a multivariable analysis correcting for age, sex, and severity of illness.
An increased number of circulating endothelial progenitor cells in acute lung injury is associated with improved survival.
受损内皮的修复对于急性肺损伤的恢复很重要。在动物模型中,骨髓来源的内皮祖细胞可分化为成熟内皮,并协助修复受损的脉管系统。
急性肺损伤患者体内内皮祖细胞的数量尚不清楚。我们假设循环内皮祖细胞数量增加与急性肺损伤和急性呼吸窘迫综合征的预后改善相关。
采用Ficoll密度梯度离心法从早期急性肺损伤患者(n = 45)、插管对照受试者(n = 10)和健康志愿者(n = 7)的血沉棕黄层中分离外周血单个核细胞,并接种于纤连蛋白包被的培养器皿上。24小时后,去除未贴壁细胞,并以1×10(6) 个细胞/孔的浓度重新接种于纤连蛋白包被的培养器皿上。培养7天后计数集落形成单位。
测量指标/主要结果:与健康对照受试者相比,急性肺损伤患者的内皮祖细胞集落数显著更高(p < 0.05),但急性肺损伤患者与插管对照受试者之间无差异。然而,在45例急性肺损伤患者中,生存率提高与集落计数较高相关(p < 0.04)。集落计数≥35的急性肺损伤患者死亡率为30%,而集落计数<35的患者死亡率为61%(p < 0.03),在对年龄、性别和疾病严重程度进行校正的多变量分析中,该结果依然成立。
急性肺损伤时循环内皮祖细胞数量增加与生存率提高相关。