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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:746.)
© 2009 American Heart Association, Inc.

Cell Biology/Signaling

CD146 and its Soluble Form Regulate Monocyte Transendothelial Migration

Nathalie Bardin; Marcel Blot-Chabaud; Nicolas Despoix; Abdeldjalil Kebir; Karim Harhouri; Jean-Pierre Arsanto; Leon Espinosa; Pierre Perrin; Stéphane Robert; Frédéric Vely; Florence Sabatier; André Le Bivic; Gilles Kaplanski; José Sampol; Françoise Dignat-George

From UMR-S 608 INSERM (N.B., M.B.-C., N.D., A.K., K.H., P.P., S.R., F.V., F.S., G.K., J.S., F.D.-G.), Université de la Méditerranée, UFR de Pharmacie; IBDML, CNRS UMR 6216, Université de la Méditerranée (J.-P.A., A.L.); and Unité des Ricketssies, Faculté Médecine (L.E.), Marseille, France.

Correspondence to Dr N. Bardin, PhD, UMR-S 608 Laboratoire d’Hématologie et d’Immunologie, UFR de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France. E-mail nathalie.bardin{at}pharmacie.univ-mrs.fr

Objectives— 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.

Methods and 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.

Key Words: endothelial cells • inflammation • cytokines • human • adhesion molecules

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