title: Neutrophils recruit and activate human endothelial colony-forming cells at the site of vessel injury via P-selectin glycoprotein ligand-1 and L-selectin.
abstract: BACKGROUND
  Endothelial colony-forming cells (ECFCs) represent a subpopulation of circulating endothelial progenitor cells that have been implicated in vascular repair. However, no study has evaluated the role of ECFCs in endothelial injury leading to thrombus formation.
  
  
  OBJECTIVE
  We investigated the kinetics, mechanisms and role of ECFC recruitment in the dynamics of thrombus formation and stabilization.
  
  
  RESULTS
  Using digital intravital microscopy in living mice, we show that ECFCs, but not mature endothelial cells, adhere to sites of laser-induced injury and do not affect the kinetics of thrombus formation. This interaction occurs once the platelet thrombus has been stabilized, and is dependent on the presence of neutrophils but not platelets or fibrin. In vitro, the interaction of the activated neutrophils with activated endothelial cells is a prerequisite for the capture of ECFCs. Neutrophils activate ECFCs and increase their angiogenic properties, such as their ability to migrate and to form pseudocapillaries. This newly identified interaction of ECFCs with the neutrophils is mediated by the P-selectin glycoprotein ligand-1 (PSGL-1)/L-selectin axis both in vitro and in vivo.
  
  
  CONCLUSIONS
  This study is the first demonstration that neutrophils present at the site of injury recruit ECFCs via PSGL-1/L-selectin. This interaction between neutrophils and ECFCs could play a key role in the regeneration of injured vessels in pathophysiologic conditions.
authors.affiliation: Aix Marseille Université, VRCM INSERM UMR-S1076, Marseille, France.
authors.forename: L
authors.initials: L
authors.lastname: Hubert
authors.forename: R
authors.initials: R
authors.lastname: Darbousset
authors.forename: L
authors.initials: L
authors.lastname: Panicot-Dubois
authors.forename: S
authors.initials: S
authors.lastname: Robert
authors.forename: F
authors.initials: F
authors.lastname: Sabatier
authors.forename: K
authors.initials: K
authors.lastname: Fallague
authors.forename: F
authors.initials: F
authors.lastname: Dignat-George
authors.forename: C
authors.initials: C
authors.lastname: Dubois
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology; D002448:Cell Adhesion; D042783:Endothelial Cells / Q000166:cytology; D004727:Endothelium / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology*; D005312:Fetal Blood / Q000166:cytology; D005337:Fibrin / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D019041:L-Selectin / Q000378:metabolism*; D007834:Lasers; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008853:Microscopy; D009504:Neutrophils / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D013927:Thrombosis / Q000473:pathology; D014945:Wound Healing
chemical_list: D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D034741:RNA, Small Interfering; D019041:L-Selectin; D005337:Fibrin
keywords: animal models; hematopoietic stem cells; neutrophils; platelet; thrombosis