title: Vascular Repair by Tissue-Resident Endothelial Progenitor Cells in Endotoxin-Induced Lung Injury.
abstract: Vascular disruption is one of the pathological hallmarks in acute respiratory distress syndrome. Bone marrow (BM)-derived circulating endothelial progenitor cells (EPCs) and lung tissue-resident EPCs have been considered to play a pivotal role in pulmonary vascular repair; however, which population is predominant in local pulmonary vasculogenesis remains to be clarified. We therefore examined the origin of EPCs participating in the regenerative process of pulmonary vascular endothelial cells (PVECs) in experimental acute respiratory distress syndrome. Lung samples from mice administered LPS intratracheally were investigated for cell dynamics and EPC functions. Quantitative flow cytometric analysis demonstrated that the number of PVECs decreased by roughly 20% on Day 1 and then recovered on Day 7 of LPS challenge. Bromodeoxyuridine-incorporation assays and immunofluorescence microscopy demonstrated that proliferating PVECs preferentially located in the capillary vessels. Experiments using BM chimera mice revealed that most of the regenerating PVECs were tissue-resident cells, and BM-derived cells hardly engrafted as PVECs. The population of circulating putative phenotypical EPCs decreased during the first week after LPS challenge. The regenerating PVECs were characterized by high colony-forming and vasculogenic capacities, intracellular reactive oxygen species scavenging and aldehyde dehydrogenase activites, and enhanced gene expression of Abcb1b (a drug-resistant gene), suggesting that the population of PVECs included tissue-resident EPCs activated during regenerative process of PVECs. The proliferating PVECs expressed CD34, Flk-1/KDR, and c-kit more strongly and Prom1/CD133 less strongly on the surface than nonproliferating PVECs. Our findings indicated that lung tissue-resident EPCs predominantly contribute to pulmonary vascular repair after endotoxin-induced injury.
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawasaki
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Nishiwaki
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Sekine
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Rintaro
authors.initials: R
authors.lastname: Nishimura
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Suda
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Urushibara
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Takayanagi
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Terada
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Sakao
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tatsumi
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000276:immunology / Q000503:physiopathology; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D055370:Lung Injury / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D017382:Reactive Oxygen Species; D012128:Respiratory Distress Syndrome / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D014945:Wound Healing
chemical_list: D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D000444:Aldehyde Dehydrogenase
keywords: LPS; acute respiratory distress syndrome; endothelial progenitor cells; endothelial repair; vascular regeneration