CD146 and its soluble form regulate monocyte transendothelial migration.
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.
Bardin
Nathalie
N
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
Blot-Chabaud
Marcel
M
Despoix
Nicolas
N
Kebir
Abdeldjalil
A
Harhouri
Karim
K
Arsanto
Jean-Pierre
JP
Espinosa
Leon
L
Perrin
Pierre
P
Robert
Stéphane
S
Vely
Frédéric
F
Sabatier
Florence
F
Le Bivic
André
A
Kaplanski
Gilles
G
Sampol
José
J
Dignat-George
Françoise
F
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
D051929:CD146 Antigen; C497902:MCAM protein, human; D014409:Tumor Necrosis Factor-alpha