DNAM-1 and PVR Regulate Monocyte Migration through Endothelial Junctions

作者：Nicolas Reymond, Anne-Marie Imbert, Élisabeth Devilard, Stéphanie Fabre, Christian Chabannon, Luc Xerri, Catherine Farnarier, Claudia Cantoni, Cristina Bottino, Alessandro Moretta, Patrice Dubreuil, Marc Lopez · 发表于：The Journal of Experimental Medicine · 年份：2004 · DOI：10.1084/jem.20032206 · 被引用次数：282 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、Immune cells in cancer

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.