title: Fractalkine expression induces endothelial progenitor cell lysis by natural killer cells.
abstract: BACKGROUND
  Circulating CD34(+) cells, a population that includes endothelial progenitors, participate in the maintenance of endothelial integrity. Better understanding of the mechanisms that regulate their survival is crucial to improve their regenerative activity in cardiovascular and renal diseases. Chemokine-receptor cross talk is critical in regulating cell homeostasis. We hypothesized that cell surface expression of the chemokine fractalkine (FKN) could target progenitor cell injury by Natural Killer (NK) cells, thereby limiting their availability for vascular repair.
  
  
  RESULTS
  We show that CD34(+)-derived Endothelial Colony Forming Cells (ECFC) can express FKN in response to TNF-α and IFN-γ inflammatory cytokines and that FKN expression by ECFC stimulates NK cell adhesion, NK cell-mediated ECFC lysis and microparticles release in vitro. The specific involvement of membrane FKN in these processes was demonstrated using FKN-transfected ECFC and anti-FKN blocking antibody. FKN expression was also evidenced on circulating CD34(+) progenitor cells and was detected at higher frequency in kidney transplant recipients, when compared to healthy controls. The proportion of CD34(+) cells expressing FKN was identified as an independent variable inversely correlated to CD34(+) progenitor cell count. We further showed that treatment of CD34(+) circulating cells isolated from adult blood donors with transplant serum or TNF-α/IFN-γ can induce FKN expression.
  
  
  CONCLUSIONS
  Our data highlights a novel mechanism by which FKN expression on CD34(+) progenitor cells may target their NK cell mediated killing and participate to their immune depletion in transplant recipients. Considering the numerous diseased contexts shown to promote FKN expression, our data identify FKN as a hallmark of altered progenitor cell homeostasis with potential implications in better evaluation of vascular repair in patients.
authors: Aix-Marseille University, Laboratoire de Physiopathologie de l'Endothélium-UMR-S 608 INSERM, 13005, Marseille, France.
authors: Dilyana
authors: D
authors: Todorova
authors: Florence
authors: F
authors: Sabatier
authors: Evelyne
authors: E
authors: Doria
authors: Luc
authors: L
authors: Lyonnet
authors: Henri
authors: H
authors: Vacher Coponat
authors: Stéphane
authors: S
authors: Robert
authors: Nicolas
authors: N
authors: Despoix
authors: Tristan
authors: T
authors: Legris
authors: Valérie
authors: V
authors: Moal
authors: Anderson
authors: A
authors: Loundou
authors: Sophie
authors: S
authors: Morange
authors: Yvon
authors: Y
authors: Berland
authors: Francoise Dignat
authors: FD
authors: George
authors: Stéphane
authors: S
authors: Burtey
authors: Pascale
authors: P
authors: Paul
mesh_terms: D002448:Cell Adhesion; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology*; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054428:Chemokine CX3CL1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma