DNAM-1 and PVR regulate monocyte migration through endothelial junctions

Nicolas Reymond, Anne Marie Imbert, Elisabeth Devilard, Stéphanie Fabre, Christian Chabannon, Luc Xerri, Catherine Farnarier, Claudia Cantoni, Cristina Bottino, Alessandro Moretta, Patrice Dubreuil, Marc Lopez

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1331-1341
Number of pages11
JournalJournal of Experimental Medicine
Volume199
Issue number10
DOIs
Publication statusPublished - May 17 2004

Keywords

  • CD155
  • CD226
  • Diapedesis
  • Endothelium
  • Nectin

ASJC Scopus subject areas

  • Immunology

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    Reymond, N., Imbert, A. M., Devilard, E., Fabre, S., Chabannon, C., Xerri, L., Farnarier, C., Cantoni, C., Bottino, C., Moretta, A., Dubreuil, P., & Lopez, M. (2004). DNAM-1 and PVR regulate monocyte migration through endothelial junctions. Journal of Experimental Medicine, 199(10), 1331-1341. https://doi.org/10.1084/jem.20032206