DNAM-1 and PVR regulate monocyte migration through endothelial junctions.
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.
Reymond
Nicolas
N
Institut National de la Santé et de la Recherche Médicale UMR599, Institut de Cancérologie de Marseille, IFR 137, 27 Bd. Lei-Roure, 13009 Marseille, France.
Imbert
Anne-Marie
AM
Devilard
Elisabeth
E
Fabre
Stéphanie
S
Chabannon
Christian
C
Xerri
Luc
L
Farnarier
Catherine
C
Cantoni
Claudia
C
Bottino
Cristina
C
Moretta
Alessandro
A
Dubreuil
Patrice
P
Lopez
Marc
M
D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D016238:Cytapheresis; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D011991:Receptors, Virus / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology; D014471:Umbilical Veins; D000098862:T Lineage-Specific Activation Antigen 1
D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D017931:DNA Primers; D008565:Membrane Proteins; D011991:Receptors, Virus; C066100:poliovirus receptor