title: VEGF-A-induced chemotaxis of CD16+ monocytes is decreased secondary to lower VEGFR-1 expression.
abstract: BACKGROUND
  Monocyte recruitment into the vessel wall is a crucial initial step in vascular repair, arteriogenesis and atherogenesis. Two distinct human monocyte subpopulations can be classified according to their CD14/16 surface expression, namely CD14++CD16-monocytes (CD16-mo) and CD14+CD16+ monocytes (CD16+mo). We investigated different functional properties of the two monocyte subsets.
  
  
  METHODS
  CD16-/CD16+mo were isolated from human blood by an immunological selection. We assessed monocyte chemokinesis, chemotaxis, adhesion and Vascular-Endothelial Growth Factor (VEGF) receptor expression. Furthermore, generation of reactive oxygen species (ROS) as well as expression of antioxidant enzymes was investigated.
  
  
  RESULTS
  Chemokinesis of CD16+mo was decreased compared to CD16-mo (p<0.01). Likewise, adhesion capacity of CD16+mo was weaker (p<0.05). CD16+mo chemotaxis towards the angiogenic ligands vascular endothelial growth factor-A (VEGF-A) and placenta growth factor-1 (PlGF-1) was reduced compared to CD16-mo. VEGFR-1 is the receptor for VEGF-A and PlGF-1 on monocytes. VEGFR-1 protein expression was lower in CD16+mo than in CD16-mo (p<0.05). The impaired VEGF-A- and PlGF-1-induced CD16+mo chemotaxis might therefore be attributed to the reduced VEGFR-1 expression. CD16+mo exhibited less spontaneous ROS production than CD16-mo. Additionally, the antioxidant enzyme manganese superoxide dismutase was expressed at higher levels in CD16+mo (p<0.05); this might partly explain the higher oxidative resistance of CD16+mo.
  
  
  CONCLUSIONS
  These novel functional differences between CD16-mo and CD16+mo may predict different functional roles of both monocyte subsets in vascular repair, arteriogenesis and atherogenesis.
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Frauke S
authors.initials: FS
authors.lastname: Czepluch
authors.forename: Servé
authors.initials: S
authors.lastname: Olieslagers
authors.forename: Ruud
authors.initials: R
authors.lastname: van Hulten
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Vöö
authors.forename: Johannes
authors.initials: J
authors.lastname: Waltenberger
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis*
chemical_list: D018950:Lipopolysaccharide Receptors; D017382:Reactive Oxygen Species; D017452:Receptors, IgG; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1