Altered progenitor cell and cytokine profiles in bronchiolitis obliterans syndrome
Altered progenitor cell and cytokine profiles in bronchiolitis obliterans syndrome
复制标题
DOI：
10.1016/j.healun.2011.11.012
复制
发表时间：
2012-02-01
影响因子：
8.9
通讯作者：
Waddell, Thomas K.
中科院分区：
文献类型：
--
作者：
Gilpin, Sarah E.;Lung, Kalvin C.;Waddell, Thomas K.
背景：骨髓来源的祖细胞可能在肺修复和纤维化中起关键作用。CD 45（+）胶原-1（+）纤维细胞对纤维化的贡献已在其他地方被记录，最近鉴定的由Clara细胞分泌蛋白（CCSP+）标记的上皮样祖细胞可能在肺损伤后具有保护作用。这些人群之间的相互作用尚未在肺移植后闭塞性细支气管炎综合征（BOS）中进行研究。方法：采用横断面设计，通过流式细胞术分析血液样本中CCSP+细胞和CD 45（+）胶原-1（+）纤维细胞。结果：BUS级患者循环纤维细胞比例高于BOS 0级患者（p <0.05）。与此同时，与BOS 0（p）和非移植对照组相比，BOS ≥ 1患者中CCSP+细胞的比例较低，导致两组之间的细胞比例改变。根据FEV 1和FEV 1/FVC比值，CD 45（+）胶原蛋白-1（+）与CCSP+细胞的比率较高与气流受限程度较大相关。血浆分析显示两组移植后关键干细胞和炎性细胞因子增加，而基质衍生因子-1和血管内皮生长因子在BOS >= 1的情况下增加。血浆基质衍生因子-1水平也与fibrocytes post-transplantation.Conclusions：总体而言，改变祖细胞配置文件中发现的患者谁开发先进的总线，这可能是介导的循环细胞因子的改变。最终，祖细胞谱的测量可能导致进一步了解肺移植后气流阻塞的发病机制。J Heart Lung Transplant 2012;31：222-8（C）2012国际心肺移植学会。All rights reserved.
BACKGROUND: Bone marrow derived progenitor cells may play a key role in both lung repair and in fibrogenesis. The contribution of CD45(+)collagen-1(+) fibrocytes to fibrosis has been documented elsewhere and recently identified epithelial-like progenitor cells marked by Clara cell secretory protein (CCSP+) may be protective after lung injury. Interplay between these populations has not yet been studied in bronchiolitis obliterans syndrome (BOS) post-lung transplant.METHODS: In a cross-sectional design, blood samples were analyzed for CCSP+ cells and CD45(+)collagen-1(+) fibrocytes by flow cytometry. Plasma cytokines were analyzed by multiplex array.RESULTS: A higher proportion of circulating fibrocytes was measured in patients with BUS Grade than in those with BOS Grade 0(p). In parallel, a lower proportion of CCSP+ cells was found in BOS >= 1 patients compared with BOS 0(p) and non-transplant controls, resulting in an altered cell ratio between the groups. A higher ratio of CD45(+)collagen-1(+) to CCSP+ cells was associated with greater airflow limitation based on FEV1 and FEV1/FVC ratio. No relationship between cell profiles and time post-transplant was found. Plasma analysis showed an increase in key stem cell and inflammatory cytokines in both groups post-transplant, whereas stromal-derived factor-1 and vascular endothelial growth factor were increased in cases of BOS >= 1 specifically. Plasma stromal-derived factor-1 levels also correlated with fibrocytes post-transplant.CONCLUSIONS: Overall, altered progenitor cell profiles were found in patients who developed advanced BUS, which may be mediated by alterations in circulating cytokines. Ultimately, measurement of progenitor cell profiles may lead to further insight into the pathogenesis of airflow obstruction after lung transplantation. J Heart Lung Transplant 2012;31:222-8 (C) 2012 International Society for Heart and Lung Transplantation. All rights reserved.