title: Distinct CD11b+-monocyte subsets accelerate endothelial cell recovery after acute and chronic endothelial cell damage.
abstract: BACKGROUND
  Endothelial cell recovery requires replenishment of primary cells from the endothelial lineage. However, recent evidence suggests that cells of the innate immune system enhance endothelial regeneration.
  
  
  RESULTS
  Focusing on mature CD11b+-monocytes, we analyzed the fate and the effect of transfused CD11b+-monocytes after endothelial injury in vivo. CD11b-diphtheria-toxin-receptor-mice--a mouse model in which administration of diphtheria toxin selectively eliminates endogenous monocytes and macrophages--were treated with WT-derived CD11b+-monocytes from age-matched mice. CD11b+-monocytes improved endothelium-dependent vasoreactivity after 7 days while transfusion of WT-derived CD11b--cells had no beneficial effect on endothelial function. In ApoE-/--CD11b-DTR-mice with a hypercholesterolemia-induced chronic endothelial injury transfusion of WT-derived CD11b+-monocytes stimulated by interferon-γ (IFNγ) decreased endothelial function, whereas interleukin-4-stimulated (IL4) monocytes had no detectable effect on vascular function. Bioluminescent imaging revealed restriction of transfused CD11b+-monocytes to the endothelial injury site in CD11b-DTR-mice depleted of endogenous monocytes. In vitro co-culture experiments revealed significantly enhanced regeneration properties of human endothelial outgrowth cells (EOCs) when cultured with preconditioned-media (PCM) or monocytes of IL4-stimulated-subsets compared to the effects of IFNγ-stimulated monocytes.
  
  
  CONCLUSIONS
  CD11b+-monocytes play an important role in endothelial cell recovery after endothelial injury by homing to the site of vascular injury, enhancing reendothelialization and improving endothelial function. In vitro experiments suggest that IL4-stimulated monocytes enhance EOC regeneration properties most likely by paracrine induction of proliferation and cellular promotion of differentiation. These results underline novel insights in the biology of endothelial regeneration and provide additional information for the treatment of vascular dysfunction.
authors.affiliation: Medizinische Klinik und Poliklinik II, Innere Medizin, Universitätsklinikum Bonn, Germany.
authors.forename: Ulrich M
authors.initials: UM
authors.lastname: Becher
authors.affiliation: Medizinische Klinik und Poliklinik II, Innere Medizin, Universitätsklinikum Bonn, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Möller
authors.affiliation: Medizinische Klinik und Poliklinik II, Innere Medizin, Universitätsklinikum Bonn, Germany.
authors.forename: Vedat
authors.initials: V
authors.lastname: Tiyerili
authors.affiliation: Medizinische Klinik und Poliklinik II, Innere Medizin, Universitätsklinikum Bonn, Germany.
authors.forename: Mariuca
authors.initials: M
authors.lastname: Vasa Nicotera
authors.affiliation: Medizinische Klinik und Poliklinik II, Innere Medizin, Universitätsklinikum Bonn, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Hauptmann
authors.affiliation: Institut für Pharmakologie und Toxikologie, Universitätsklinikum Bonn, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Zimmermann
authors.affiliation: Institut für Pharmakologie und Toxikologie, Universitätsklinikum Bonn, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pfeifer
authors.affiliation: Medizinische Klinik und Poliklinik II, Innere Medizin, Universitätsklinikum Bonn, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Nickenig
authors.affiliation: Kardiologische Abteilung, Innere Medizin, Isarklinik München, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Wassmann
authors.affiliation: Medizinische Klinik und Poliklinik II, Innere Medizin, Universitätsklinikum Bonn, Germany. Electronic address: nikos.werner@ukb.uni-bonn.de.
authors.forename: Nikos
authors.initials: N
authors.lastname: Werner
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000502:physiology*; D020212:Carotid Artery Injuries / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000502:physiology* / Q000637:transplantation*; D009924:Organ Culture Techniques
chemical_list: D039481:CD11b Antigen
keywords: CD11b(+)-monocytes; CD11b-DTR-mice; Endothelial regeneration; Transfusion