Mao Sun-Zhong, Ye Xiaobing, Liu Gang, Song Dongmei, Liu Shu Fang
Centers for Heart and Lung Research and Pulmonary and Critical Care Medicine, the Feinstein Institute for Medical Research, Manhasset, New York, United States of America; Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Centers for Heart and Lung Research and Pulmonary and Critical Care Medicine, the Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
PLoS One. 2014 Oct 21;9(10):e111087. doi: 10.1371/journal.pone.0111087. eCollection 2014.
Recruitment of bone marrow derived endothelial progenitor cells (BMDEPCs) alleviates multiple organ injury (MOI) and improves outcomes. However, mechanisms mediating BMDEPC recruitment following septic MOI remain largely unknown. This study characterized the kinetics of BMDEPC recruitment and proliferation and defined the role of NF-κB in regulating BMDEPC recruitment and proliferation.
Chimeric mice with an intact or disrupted NF-κB p50 gene and BMDEPC-restricted expression of green fluorescent protein were created and injected with LPS (2 mg/kg, i.p.). BMDEPC recruitment and proliferation in multiple organs were quantified. BMDEPC recruitment and proliferation are highly organ-dependent. Lungs had the highest number of BMDEPC recruitment, whereas heart, liver and kidney had only a small fraction of the number of BMDEPCs in lungs. Number of proliferating BMDEPCs was several-fold higher in lungs than in other 3 organs. Kinetically, BMDEPC recruitment into different organs showed different time course profiles. NF-κB plays obligatory roles in mediating BMDEPC recruitment and proliferation. Universal deletion of NF-κB p50 gene inhibited LPS-induced BMDEPC recruitment and proliferation by 95% and 69% in heart. However, the contribution of NF-κB to these regulations varies significantly between organs. In liver, universal p50 gene deletion reduced LPS-induced BMDEPC recruitment and proliferation only by 49% and 35%. NF-κB activities in different tissue compartments play distinct roles. Selective p50 gene deletion either in stromal/parenchymal cells or in BM/blood cells inhibited BMDEPC recruitment by a similar extent. However, selective p50 gene deletion in BM/blood cells inhibited, but in stromal/parenchymal cells augmented BMDEPC proliferation.
BMDEPC recruitment and proliferation display different kinetics in different organs following endotoxemic MOI. NF-κB plays obligatory and organ-dependent roles in regulating BMDEPC recruitment and proliferation. NF-κB activities in different tissue compartments play distinct roles in regulating BMDEPC proliferation.
募集骨髓来源的内皮祖细胞（BMDEPCs）可减轻多器官损伤（MOI）并改善预后。然而，脓毒症性多器官损伤后介导BMDEPC募集的机制仍不清楚。本研究对BMDEPC募集和增殖的动力学进行了表征，并确定了NF-κB在调节BMDEPC募集和增殖中的作用。
构建了具有完整或缺失NF-κB p50基因且BMDEPC特异性表达绿色荧光蛋白的嵌合小鼠，并腹腔注射脂多糖（LPS，2mg/kg）。对多个器官中BMDEPC的募集和增殖进行定量分析。BMDEPC的募集和增殖高度依赖器官。肺中BMDEPC募集数量最多，而心脏、肝脏和肾脏中BMDEPC的数量仅为肺中的一小部分。肺中增殖的BMDEPC数量比其他三个器官高几倍。从动力学角度看，BMDEPC向不同器官的募集呈现不同的时间进程。NF-κB在介导BMDEPC募集和增殖中起关键作用。NF-κB p50基因的普遍缺失使LPS诱导的心脏中BMDEPC募集和增殖分别减少95%和69%。然而，NF-κB对这些调节的作用在不同器官之间有显著差异。在肝脏中，p50基因的普遍缺失仅使LPS诱导的BMDEPC募集和增殖分别减少49%和35%。不同组织区室中的NF-κB活性发挥不同作用。在基质/实质细胞或骨髓/血细胞中选择性缺失p50基因对BMDEPC募集的抑制程度相似。然而，在骨髓/血细胞中选择性缺失p50基因会抑制BMDEPC增殖，而在基质/实质细胞中则会增强BMDEPC增殖。
内毒素血症性多器官损伤后，BMDEPC在不同器官中的募集和增殖表现出不同的动力学。NF-κB在调节BMDEPC募集和增殖中起关键且依赖器官的作用。不同组织区室中的NF-κB活性在调节BMDEPC增殖中发挥不同作用。
