Circulating Progenitor Epithelial Cells Traffic via CXCR4/CXCL12 in Response to Airway Injury1
Circulating Progenitor Epithelial Cells Traffic via CXCR4/CXCL12 in Response to Airway Injury1
复制标题
循环祖上皮细胞通过 CXCR4/CXCL12 运输以响应气道损伤1
作者：
B. Gomperts;J. Belperio;P. Rao;S. Randell;M. Fishbein;M. Burdick;R. Strieter
在人类性别不匹配的肺移植中发现了受体气道上皮细胞，这表明循环祖上皮细胞有助于气道上皮的修复。循环祖上皮细胞的标志物及其运输机制仍有待阐明。我们证明，在骨髓和小鼠循环中存在一群祖上皮细胞，其早期上皮标志物细胞角蛋白5 （CK5）和趋化因子受体CXCR4呈阳性。我们使用小鼠性别不匹配气管移植模型，发现CK5+循环祖上皮细胞有助于气道的再上皮化和假分层上皮的重建。气管移植中CXCL12的存在为CXCR4+循环祖上皮细胞向气道募集提供了一种机制。CXCL12的缺失导致上皮默认为鳞状化生，而鳞状化生仅来源于常驻组织祖上皮细胞。我们的研究结果表明，CK5+CXCR4+细胞是骨髓和循环中循环祖上皮细胞的标志物，并且CXCR4/ cxcl12介导的循环祖上皮细胞募集对于气道损伤后重建正常的假分层上皮是必要的。这些发现为气道上皮鳞状化生的发展和气道疾病中循环祖上皮细胞的治疗策略的发展提供了新的范例。
Recipient airway epithelial cells are found in human sex-mismatched lung transplants, implying that circulating progenitor epithelial cells contribute to the repair of the airway epithelium. Markers of circulating progenitor epithelial cells and mechanisms for their trafficking remain to be elucidated. We demonstrate that a population of progenitor epithelial cells exists in the bone marrow and the circulation of mice that is positive for the early epithelial marker cytokeratin 5 (CK5) and the chemokine receptor CXCR4. We used a mouse model of sex-mismatched tracheal transplantation and found that CK5+ circulating progenitor epithelial cells contribute to re-epithelialization of the airway and re-establishment of the pseudostratified epithelium. The presence of CXCL12 in tracheal transplants provided a mechanism for CXCR4+ circulating progenitor epithelial cell recruitment to the airway. Depletion of CXCL12 resulted in the epithelium defaulting to squamous metaplasia, which was derived solely from the resident tissue progenitor epithelial cells. Our findings demonstrate that CK5+CXCR4+ cells are markers of circulating progenitor epithelial cells in the bone marrow and circulation and that CXCR4/CXCL12-mediated recruitment of circulating progenitor epithelial cells is necessary for the re-establishment of a normal pseudostratified epithelium after airway injury. These findings support a novel paradigm for the development of squamous metaplasia of the airway epithelium and for developing therapeutic strategies for circulating progenitor epithelial cells in airway diseases.
登录
查看更多内容
DOI：
10.1165/rcmb.2002-0056rc
发表时间：
2002-12-01
影响因子：
6.4
作者：
Grove, JE;Lutzko, C;Krause, DS
通讯作者：
Krause, DS
DOI：
10.1172/jci17902
发表时间：
2003-07
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
O. Kollet;Shoham Shivtiel;Yuan-Qing Chen;Jenny Suriawinata;S. Thung;M. Dabeva;J. Kahn;Asaf Spiegel-Asaf-Spie
通讯作者：
O. Kollet;Shoham Shivtiel;Yuan-Qing Chen;Jenny Suriawinata;S. Thung;M. Dabeva;J. Kahn;Asaf Spiegel-Asaf-Spie
影响因子：
2.6
作者：
Theise, ND;Henegariu, O;Krause, DS
通讯作者：
Krause, DS
影响因子：
6
作者：
Hong, KU;Reynolds, SD;Stripp, BR
通讯作者：
Stripp, BR
影响因子：
15.9
作者：
Belperio, JA;Keane, MP;Strieter, RM
通讯作者：
Strieter, RM