title: Resident Endothelial Cells and Endothelial Progenitor Cells Restore Endothelial Barrier Function After Inflammatory Lung Injury.
abstract: OBJECTIVE
  Disruption of endothelial barrier integrity is a characteristic of many inflammatory conditions. However, the origin and function of endothelial cells (ECs) restoring endothelial barrier function remain unknown. This study defined the roles of resident ECs (RECs) and bone marrow-derived endothelial progenitor cells (BMDEPCs) in endothelial barrier restoration after endotoxemic lung injury.
  
  
  RESULTS
  We generated mice that enable to quantify proliferating RECs or BMDEPCs and also to study the causal link between REC or BMDEPC proliferation and endothelial barrier restoration. Using these mouse models, we showed that endothelial barrier restoration was associated with increased REC and BMDEPC proliferation. RECs and BMDEPCs participate in barrier repair. Immunofluorescence staining demonstrated that RECs proliferate in situ on endothelial layer and that BMDEPCs are engrafted into endothelial layer of lung microvessels at the active barrier repair phase. In lungs, 8 weeks after lipopolysaccharide-induced injury, the number of REC-derived ECs (CD45(-)/CD31(+)/BrdU(+)/rtTA(+)) or BMDEPC-derived ECs (CD45(-)/CD31(+)/eNOS(+)/GFP(+)) increased by 22- or 121-fold, respectively. The suppression of REC or BMDEPC proliferation by blocking REC or BMDEPC intrinsic nuclear factor-κB at the barrier repair phase was associated with an augmented endothelial permeability and impeded endothelial barrier recovery. RECs and BMDEPCs contributed differently to endothelial barrier repair. In lungs, 8 weeks after lipopolysaccharide-induced injury, REC-derived ECs constituted 22%, but BMDEPC-derived ECs constituted only 3.7% of the total new ECs.
  
  
  CONCLUSIONS
  REC is a major and BMDEPC is a complementary source of new ECs in endothelial barrier restoration. RECs and BMDEPCs play important roles in endothelial barrier restoration after inflammatory lung injury.
authors.affiliation: Centers for Heart and Lung Research, and Pulmonary and Critical Care Medicine, the Feinstein Institute for Medical Research, Manhasset, NY 11030, U.S.A.|Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Sun-Zhong
authors.initials: SZ
authors.lastname: Mao
authors.affiliation: Centers for Heart and Lung Research, and Pulmonary and Critical Care Medicine, the Feinstein Institute for Medical Research, Manhasset, NY 11030, U.S.A.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Ye
authors.affiliation: Centers for Heart and Lung Research, and Pulmonary and Critical Care Medicine, the Feinstein Institute for Medical Research, Manhasset, NY 11030, U.S.A.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Centers for Heart and Lung Research, and Pulmonary and Critical Care Medicine, the Feinstein Institute for Medical Research, Manhasset, NY 11030, U.S.A.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Song
authors.affiliation: Centers for Heart and Lung Research, and Pulmonary and Critical Care Medicine, the Feinstein Institute for Medical Research, Manhasset, NY 11030, U.S.A.|Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Shu Fang
authors.initials: SF
authors.lastname: Liu
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology*; D066026:Endothelial Progenitor Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D055370:Lung Injury / Q000473:pathology* / Q000503:physiopathology*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D016328:NF-kappa B
keywords: NF-κB; endothelial cells