He Shengdong, He Zhihui, Chen Yan, Ye Jiru, Zong Dandan, Zhang Yan, Chen Ping
Department of Pulmonary Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.
Exp Lung Res. 2013 Aug;39(6):258-67. doi: 10.3109/01902148.2013.802828. Epub 2013 Jun 20.
Smoking causes lung endothelial cell apoptosis and emphysema. Derived from bone marrow, circulating endothelial progenitor cells (EPCs) maintain vascular integrity by replacing and repairing damaged endothelial cells. Smoking influences the number of circulating EPCs. Recruitment of EPCs from bone marrow to peripheral blood depends on the interaction of c-Kit/soluble c-Kit ligand (sKitL). We hypothesized that smoking might influence c-Kit(+) EPCs/sKitL interaction in bone marrow in the development of smoking-related emphysema. In this study, we used a cigarette smoke extract (CSE)-induced emphysema model.
Mice were injected intraperitoneally with PBS/CSE and sacrificed at day 28. Lung function and pathology of lung tissue were measured to characterize the model. Expressions of c-Kit in the lung tissue were assayed. Bone marrow cells were isolated by red blood cell lysis. EPCs/c-Kit(+) EPCs in nonred blood cells were analyzed by flow cytometry. Expressions of KitL and MMP-9, and activity MMP-9 in bone marrow were measured.
Our data demonstrated that gene and protein expressions of c-Kit were decreased in the lung tissue in this model. Compared with the control group, the number of bone marrow nonred blood cells was unchanged following CSE treatment, while the depletion of bone marrow EPCs/c-Kit(+) EPCs was significant. The level of sKitL was reduced in the bone marrow in the model. The reduction of sKitL was associated with deregulated KitL expression and decreased MMP-9 activity.
The interaction between c-Kit and sKitL in bone marrow EPCs, a critical step in endothelial repair, is negatively affected in a CSE-induced emphysema model.
吸烟会导致肺内皮细胞凋亡和肺气肿。循环内皮祖细胞（EPCs）来源于骨髓，通过替代和修复受损的内皮细胞来维持血管完整性。吸烟会影响循环EPCs的数量。EPCs从骨髓募集到外周血取决于c-Kit/可溶性c-Kit配体（sKitL）的相互作用。我们推测吸烟可能在吸烟相关肺气肿的发展过程中影响骨髓中c-Kit(+) EPCs/sKitL的相互作用。在本研究中，我们使用了香烟烟雾提取物（CSE）诱导的肺气肿模型。
给小鼠腹腔注射PBS/CSE，并在第28天处死。测量肺功能和肺组织病理学以表征该模型。检测肺组织中c-Kit的表达。通过红细胞裂解分离骨髓细胞。通过流式细胞术分析非红细胞中的EPCs/c-Kit(+) EPCs。测量骨髓中KitL和MMP-9的表达以及MMP-9的活性。
我们的数据表明，该模型中肺组织中c-Kit的基因和蛋白表达降低。与对照组相比，CSE处理后骨髓非红细胞数量未变，而骨髓EPCs/c-Kit(+) EPCs的减少显著。模型中骨髓中sKitL水平降低。sKitL的降低与KitL表达失调和MMP-9活性降低有关。
在CSE诱导的肺气肿模型中，骨髓EPCs中c-Kit与sKitL之间的相互作用（内皮修复的关键步骤）受到负面影响。
