Acute Lung Injury but Not Sepsis Is Associated with Increased Colony Formation by Peripheral Blood Mononuclear Cells

Acute Lung Injury but Not Sepsis Is Associated with Increased Colony Formation by Peripheral Blood Mononuclear Cells
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DOI:
10.1165/rcmb.2009-0015oc
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发表时间:
2010-09-01
影响因子:
6.4
通讯作者:
Moss, Marc
Moss, Marc
中科院分区:
医学1区
文献类型:
--
作者:
Burnham, Ellen L.;Mealer, Meredith;Moss, Marc

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急性肺损伤(ALI)和严重脓毒症是与骨髓源性细胞动员进入循环相关的常见危重疾病。通过识别和确定这些细胞的功能特征,可以开发独特的预后生物标志物,以帮助研究人员了解这些疾病的病理生理学机制。我们以前证明了与健康对照组相比,ALI患者循环外周血单核细胞(PBMC)的集落形成单位(CFU)能力增加,这也与生存率提高相关。在此,我们假设ALI中CFU的增加与肺损伤相关,因此与严重脓毒症患者相比,ALI将导致CFU数量增加。为了测试这一点,在诊断后72小时内从80名患者(63名患有ALI,17名患有严重脓毒症)和5名健康对照受试者中收集血液。对分离的PBMCs进行了CFU测定。ALI患者的肺损伤评分和机械通气需求均高于严重脓毒症患者(均P < 0.0001)。与严重脓毒症患者或对照组相比,ALI患者的CFU数最高(CFU数中位数[25-75%四分位数]为61 [13-104] vs 17 [334] vs 5 [2-13],P < 0.0005)。在高CFU(>= 48)的患者中显示出生存率改善的趋势(P = 0.06)。CFU和机械通气之间没有明显的关系。我们的研究结果表明,肺损伤的结果,独立于败血症和机械通气的肺损伤的PBMC的集落形成能力增加。ALI患者PBMC集落形成的影响因素以及PBMC在其发病机制中的作用尚待充分研究。
Acute lung injury (ALI) and severe sepsis are common critical illnesses associated with the mobilization of bone marrow-derived cells into the circulation. By identifying and determining these cells' functional characteristics, unique prognostic biomarkers can be developed to help investigators understand the mechanisms underlying the pathophysiology of these disorders. We previously demonstrated an increased colony-forming unit (CFU) ability of circulating peripheral blood mononuclear cells (PBMCs) in patients with ALI, compared with healthy control subjects, that also correlated with improved survival. Here we hypothesized that the increased CFUs in ALI are associated with lung injury, and therefore ALI will result in an increased number of CFUs compared with patients exhibiting severe sepsis. To test this, blood was collected from 80 patients (63 with ALI, and 17 with severe sepsis) within 72 hours of diagnosis, and from 5 healthy control subjects. A CFU assay was performed on isolated PBMCs. Lung injury scores and the need for mechanical ventilation were greater in patients with ALI than in patients with severe sepsis (P < 0.0001 for each). CFU numbers were highest in patients with ALI compared with patients manifesting severe sepsis or control subjects (median CFU number [25-75% quartiles] of 61 [13-104] versus 17 [334] versus 5 [2-13], P < 0.0005). A trend toward improved survival was demonstrated in patients with high (>= 48) CFUs (P = 0.06). No relationship between CFUs and mechanical ventilation was evident. Our findings suggest that increased colony-forming ability by PBMCs in ALI results from lung injury, independent of sepsis and mechanical ventilation. Factors contributing to colony formation by PBMCs in ALI, and the role PBMCs play in its pathogenesis remain to be fully established.