title: Gremlin-1 inhibits macrophage migration inhibitory factor-dependent monocyte function and survival.
abstract: BACKGROUND
  Monocyte migration and their differentiation into macrophages critically regulate vascular inflammation and atherogenesis and are governed by macrophage migration inhibitory factor (MIF). Gremlin-1 binds to MIF. Current experimental evidences present Gremlin-1 as a potential physiological agent that might counter-regulate the inflammatory attributes of MIF.
  
  
  RESULTS
  We found that Gremlin-1 inhibited MIF-dependent monocyte migration and adhesion to activated endothelial cells in flow chamber perfusion assay in vitro and to the injured carotid artery of WT and ApoE-/- mice in vivo as deciphered by intravital microscopy. Intravenous administration of Gremlin-1, but not of control protein, significantly reduced leukocyte recruitment towards the inflamed carotid artery of ApoE-/- mice. Besides, leukocytes from MIF-/- when administered into ApoE-/- mice showed lesser adhesion as compared to wild type. In the presence of Gremlin-1 however, adhesion of wild type, but not of MIF-/- leukocytes, to the carotid artery was significantly inhibited as compared to control. Gremlin-1 also inhibited the MIF-induced differentiation of monocytes into macrophages. Gremlin-1 substantially inhibited the anti-apoptotic impact of MIF on monocytes against BH3 mimetic ABT-737-induced apoptosis as verified by Annexin V-binding, caspase 3 activity, and mitochondrial depolarization.
  
  
  CONCLUSIONS
  Therefore Gremlin-1 can modulate MIF dependent monocyte adhesion, migration, differentiation and survival.
authors.affiliation: Innere Medizin III, Kardiologie und Kreislauferkrankungen, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Iris I
authors.initials: II
authors.lastname: Müller
authors.affiliation: Innere Medizin III, Kardiologie und Kreislauferkrankungen, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Madhumita
authors.initials: M
authors.lastname: Chatterjee
authors.affiliation: Innere Medizin III, Kardiologie und Kreislauferkrankungen, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Innere Medizin III, Kardiologie und Kreislauferkrankungen, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Borst
authors.affiliation: Innere Medizin III, Kardiologie und Kreislauferkrankungen, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Seizer
authors.affiliation: Innere Medizin III, Kardiologie und Kreislauferkrankungen, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schönberger
authors.affiliation: Innere Medizin III, Kardiologie und Kreislauferkrankungen, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Vogel
authors.affiliation: Innere Medizin III, Kardiologie und Kreislauferkrankungen, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Karin A L
authors.initials: KA
authors.lastname: Müller
authors.affiliation: Innere Medizin III, Kardiologie und Kreislauferkrankungen, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Geisler
authors.affiliation: Physiology Institute, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.affiliation: Innere Medizin III, Kardiologie und Kreislauferkrankungen, Eberhard Karls Universität, Tübingen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Langer
authors.affiliation: Innere Medizin III, Kardiologie und Kreislauferkrankungen, Eberhard Karls Universität, Tübingen, Germany. Electronic address: meinrad.gawaz@med.uni-tuebingen.de.
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors* / Q000502:physiology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*
chemical_list: C486399:GREM1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008263:Macrophage Migration-Inhibitory Factors
keywords: Apoptosis; Gremlin-1; MIF; Migration; Monocyte