title: CD146 and its soluble form regulate monocyte transendothelial migration.
abstract: OBJECTIVE
  During inflammation, cell adhesion molecules are modulated or redistributed for leukocyte transmigration. Among molecules at the interendothelial junction, CD146 is involved in cell-cell cohesion and permeability, but its role in monocyte transmigration is unknown.
  
  
  RESULTS
  TNF enhanced CD146 expression at the junction and apical membrane of human umbilical veins endothelial cells (HUVECs) through CD146 synthesis and intracellular store redistribution. In addition, TNF increased the release of a soluble form (sCD146) through a metalloproteinase-dependent mechanism. The redistribution of CD146 to the junction led us to investigate its role in monocyte transmigration using THP1 and freshly isolated monocytes. Evidence that CD146 contributes to monocyte transmigration was provided by inhibition experiments using anti-CD146 antibodies and CD146 siRNA in HUVECs. In addition, sCD146 specifically bound both monocytes and HUVECs and dose-dependently increased monocyte transmigration. Assessment of sCD146 binding on immobilized CD146 failed to evidence any homophilic interaction. Together, our data suggest endothelial CD146 binds heterophilically with a yet unknown ligand on monocytes.
  
  
  CONCLUSIONS
  Our results demonstrate that CD146 is regulated by the inflammatory cytokine TNF and that CD146 and sCD146 are both involved in monocyte transendothelial migration during inflammation.
authors.affiliation: UMR-S 608 INSERM, Laboratoire d'Hématologie et d'Immunologie, Université de la Méditerranée, UFR de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France. nathalie.bardin@pharmacie.univ-mrs.fr
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bardin
authors.forename: Marcel
authors.initials: M
authors.lastname: Blot-Chabaud
authors.forename: Nicolas
authors.initials: N
authors.lastname: Despoix
authors.forename: Abdeldjalil
authors.initials: A
authors.lastname: Kebir
authors.forename: Karim
authors.initials: K
authors.lastname: Harhouri
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Arsanto
authors.forename: Leon
authors.initials: L
authors.lastname: Espinosa
authors.forename: Pierre
authors.initials: P
authors.lastname: Perrin
authors.forename: Stéphane
authors.initials: S
authors.lastname: Robert
authors.forename: Frédéric
authors.initials: F
authors.lastname: Vely
authors.forename: Florence
authors.initials: F
authors.lastname: Sabatier
authors.forename: André
authors.initials: A
authors.lastname: Le Bivic
authors.forename: Gilles
authors.initials: G
authors.lastname: Kaplanski
authors.forename: José
authors.initials: J
authors.lastname: Sampol
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
mesh_terms: D051929:CD146 Antigen / Q000276:immunology; D045744:Cell Line, Tumor; D002633:Chemotaxis / Q000276:immunology*; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D051929:CD146 Antigen; C497902:MCAM protein, human; D014409:Tumor Necrosis Factor-alpha