title: Imbalance of circulating endothelial cells and progenitors in idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  Fibrogenesis during idiopathic pulmonary fibrosis (IPF) is strongly associated with abnormal vascular remodeling. Respective abundance of circulating endothelial cells (CEC) and endothelial progenitor cells (EPC) might reflect the balance between vascular injury and repair and potentially serve as biomarkers of the disease.
  
  
  OBJECTIVE
  We postulated that CEC and EPC subtypes might be differently modulated in IPF. Sixty-four consecutive patients with newly diagnosed IPF were prospectively enrolled and compared to thirteen healthy volunteers. CEC were counted with immunomagnetic CD146-coated beads; progenitors CD34+45(dim)/CD34+133+/CD34+KDR+were assessed through flow cytometry and EPC (colony-forming-units-Endothelial Cells, CFU-EC, and endothelial colonies forming cells, ECFC) were quantified by cell culture assays.
  
  
  RESULTS
  IPF patients were characterized by a marked increase in CEC associated to an EPC defect: both CD34(+)KDR(+) cells and CFU-EC were decreased versus controls. Moreover, in IPF subjects with a low diffusing capacity of the lung for carbon monoxide (DL(CO)) < 40 %, CFU-EC and ECFC were higher compared to those with DL(CO) > 40 %. Finally, ECFC were negatively correlated with DL(CO). During an 18 month follow up, CEC levels increased in patients with exacerbation, including those who died during follow up. Finally, ECFC from patients with exacerbation proliferative potential was strongly increased.
  
  
  CONCLUSIONS
  IPF is basically associated with both a vascular injury and a repair defect. This study highlights an adaptative process of EPC mobilization in the most severe forms of IPF, that could reflect enhanced homing to the pulmonary vasculature, which clinical consequences remain to be determined.
authors.affiliation: Hematology Department, European Georges Pompidou Hospital, Université Paris Descartes, France. david.smadja@egp.aphp.fr
authors.forename: David M
authors.initials: DM
authors.lastname: Smadja
authors.forename: Laetitia
authors.initials: L
authors.lastname: Mauge
authors.forename: Hilario
authors.initials: H
authors.lastname: Nunes
authors.forename: Clément
authors.initials: C
authors.lastname: d'Audigier
authors.forename: Karine
authors.initials: K
authors.lastname: Juvin
authors.forename: Raphael
authors.initials: R
authors.lastname: Borie
authors.forename: Zohra
authors.initials: Z
authors.lastname: Carton
authors.forename: Sébastien
authors.initials: S
authors.lastname: Bertil
authors.forename: Anne
authors.initials: A
authors.lastname: Blanchard
authors.forename: Bruno
authors.initials: B
authors.lastname: Crestani
authors.forename: Dominique
authors.initials: D
authors.lastname: Valeyre
authors.forename: Pascale
authors.initials: P
authors.lastname: Gaussem
authors.forename: Dominique
authors.initials: D
authors.lastname: Israel-Biet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002452:Cell Count; D002465:Cell Movement; D003710:Demography; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*