title: In vitro and in vivo effects of human monocytes and their subsets on new vessel formation.
abstract: OBJECTIVE
  Human monocytes can be divided into CD16(-) monocytes and CD16(+) monocytes. Studies in mice suggested differential effects of monocyte subsets during new vessel formation.
  
  
  METHODS
  The functional role of human monocyte subsets in neovascularization processes was investigated. For in vivo experiments, nude mice underwent unilateral hindlimb ischemia surgery before being injected with either total monocytes, CD16(-) monocytes or CD16(+) monocytes isolated from healthy individuals.
  
  
  RESULTS
  In vitro, cytokine array analysis demonstrated that monocytes release numerous angiogenic cytokines, some of which were differentially expressed in monocyte subsets. Sprout length was enhanced in EC spheroids being cultured in conditioned medium obtained from total monocytes and, to a lesser extent, also in supernatants of CD16(-) monocytes. Laser Doppler perfusion imaging up to day 28 after surgery revealed a trend toward improved revascularization in mice treated with monocytes, but no significant differences between monocyte subsets. Histological analyses four weeks after surgery showed an increased arteriole size in mice having received CD16(+) monocytes, whereas the number of capillaries did not significantly differ between groups.
  
  
  CONCLUSIONS
  Our findings suggest additive and differential effects of monocyte subsets during neovascularization processes, possibly due to an altered secretion of angiogenic factors and their paracrine capacity to stimulate new vessel formation.
authors.affiliation: Department of Cardiology and Pulmonary Medicine, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Frauke S
authors.initials: FS
authors.lastname: Czepluch
authors.forename: Markus
authors.initials: M
authors.lastname: Bernhardt
authors.forename: Hendrik
authors.initials: H
authors.lastname: Kuschicke
authors.forename: Rajinikanth
authors.initials: R
authors.lastname: Gogiraju
authors.forename: Marco R
authors.initials: MR
authors.lastname: Schroeter
authors.forename: Joachim
authors.initials: J
authors.lastname: Riggert
authors.forename: Gerd
authors.initials: G
authors.lastname: Hasenfuss
authors.forename: Katrin
authors.initials: K
authors.lastname: Schäfer
mesh_terms: D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D064593:Heterografts; D006614:Hindlimb / Q000098:blood supply; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009000:Monocytes / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D018919:Neovascularization, Physiologic
keywords: CD14; CD16; angiogenesis; arteriogenesis; blood vessel; hindlimb ischemia; monocytes