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Dnam-1 and pvr regulate monocyte migration through endothelial junctions.
| Content Provider | CiteSeerX |
|---|---|
| Author | Reymond, Nicolas Imbert, Anne-Marie Devilard, Elisabeth Fabre, Stéphanie Chabannon, Christian Xerri, Luc Farnarier, Catherine Cantoni, Claudia Bottino, Cristina Moretta, Ro Dubreuil, Patrice Lopez, Marc |
| Abstract | DNAX accessory molecule 1 (DNAM-1; CD226) is a transmembrane glycoprotein involved in T cell and natural killer (NK) cell cytotoxicity. We demonstrated recently that DNAM-1 triggers NK cell–mediated killing of tumor cells upon engagement by its two ligands, poliovirus receptor (PVR; CD155) and Nectin-2 (CD112). In the present paper, we show that PVR and Nectin-2 are expressed at cell junctions on primary vascular endothelial cells. Moreover, the specific binding of a soluble DNAM-1–Fc molecule was detected at endothelial junctions. This binding was almost completely abrogated by anti-PVR monoclonal antibodies (mAbs), but not modified by anti–Nectin-2 mAbs, which demonstrates that PVR is the major DNAM-1 ligand on endothelial cells. Because DNAM-1 is highly expressed on leukocytes, we investigated the role of the DNAM-1–PVR interaction during the monocyte transendothelial migration process. In vitro, both anti–DNAM-1 and anti-PVR mAbs strongly blocked the transmigration of monocytes through the endothelium. Moreover, after anti–DNAM-1 or anti-PVR mAb treatment, monocytes were arrested at the apical surface of the endothelium over intercellular junctions, which strongly suggests that the DNAM-1–PVR interaction occurs during the diapedesis step. Altogether, our results demonstrate that DNAM-1 regulates monocyte extravasation via its interaction with PVR expressed at endothelial junctions on normal cells. Key words: CD226 • CD155 • Nectin • endothelium • diapedesis |
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| Access Restriction | Open |
| Subject Keyword | Endothelial Junction Pvr Regulate Monocyte Migration Anti Dnam-1 Dnam-1 Pvr Interaction Endothelial Cell Intercellular Junction Primary Vascular Endothelial Cell Tumor Cell Soluble Dnam-1 Fc Molecule Apical Surface Anti-pvr Mab Treatment Monocyte Transendothelial Migration Process Anti Nectin-2 Mabs Dnam-1 Trigger Nk Cell Transmembrane Glycoprotein Cell Cytotoxicity Cd226 Cd155 Nectin Endothelium Diapedesis Specific Binding Anti-pvr Mabs Poliovirus Receptor Major Dnam-1 Ligand Natural Killer Monocyte Extravasation Anti-pvr Monoclonal Antibody Normal Cell Diapedesis Step Cell Junction Present Paper Dnax Accessory Molecule |
| Content Type | Text |
