Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, North Wing, 9N - 949, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada.
BMC Pulm Med. 2013 Aug 3;13:48. doi: 10.1186/1471-2466-13-48.
Chronic lung diseases are marked by progressive inflammation, tissue damage and remodelling. Bone marrow-derived progenitor cells may contribute to these processes. The objectives of this study were to (1) to quantify CD45⁺Collagen-1⁺ fibrocytes and a novel epithelial-like population of bone marrow-derived cells, which express Clara Cell Secretory Protein, in patients at the time of lung transplant and (2) to evaluate mediators that may act to recruit these cells during injury.
Using an observational design, progenitor cells were quantified by flow cytometry from both bone marrow (BM) and peripheral blood (PB). Migration was tested using in vitro transwell assays. Multiplex bead-based assays were used to quantify plasma cytokines.
An increase in CD45⁺Collagen-1⁺ fibrocytes was found in pulmonary fibrosis and bronchiolitis obliterans patients. Cystic fibrosis patients had an increase in CCSP⁺ cells in both the BM and PB. The proportion of CCSP⁺ cells in the BM and PB was correlated. CCSP+ cells express the chemokine receptors CCR2, CCR4, CXCR3, and CXCR4, and significantly migrated in vitro toward Stromal Derived Factor-1 (SDF-1) and Stem Cell Growth Factor-β (SCGF-β). Plasma cytokine levels differed between disease groups, with a significant correlation between SCGF-β and CCSP⁺ cells and between Monocyte Chemotactic Protein-1 and fibrocytes.
Different bone marrow-derived cells are found in various lung diseases. Increased fibrocytes were associated with fibrotic lung diseases. An increase in the novel CCSP⁺ epithelial-like progenitors in cystic fibrosis patients was found. These differences may be mediated by alterations in plasma cytokines responsible for cell recruitment.
慢性肺部疾病以进行性炎症、组织损伤和重塑为特征。骨髓源性祖细胞可能参与这些过程。本研究的目的是：（1）在肺移植时量化 CD45 ⁺ 胶原蛋白 ⁺ 成纤维细胞和一种新的表达 Clara 细胞分泌蛋白的骨髓源性细胞上皮样群体；（2）评估在损伤过程中可能招募这些细胞的介质。
采用观察性设计，通过流式细胞术从骨髓（BM）和外周血（PB）中定量祖细胞。使用体外 Transwell 测定法测试迁移。使用多重珠粒基于检测的测定法来定量血浆细胞因子。
在肺纤维化和细支气管炎性闭塞患者中发现 CD45 ⁺ 胶原蛋白 ⁺ 成纤维细胞增加。囊性纤维化患者在 BM 和 PB 中均增加了 CCSP ⁺ 细胞。BM 和 PB 中 CCSP ⁺ 细胞的比例相关。CCSP ⁺ 细胞表达趋化因子受体 CCR2、CCR4、CXCR3 和 CXCR4，并显著向基质衍生因子-1（SDF-1）和干细胞生长因子-β（SCGF-β）体外迁移。疾病组之间的血浆细胞因子水平不同，SCGF-β与 CCSP ⁺ 细胞之间以及单核细胞趋化蛋白-1 与成纤维细胞之间存在显著相关性。
在各种肺部疾病中发现了不同的骨髓源性细胞。成纤维细胞的增加与纤维性肺部疾病有关。在囊性纤维化患者中发现了新型 CCSP ⁺ 上皮样祖细胞的增加。这些差异可能是由负责细胞募集的血浆细胞因子的改变介导的。
