Sialyl Lewisx-dependent binding of human monocyte-derived dendritic cells to selectins

• Published in: Biochemical and biophysical research communications 2011-06, Vol.409 (3), p.459-464
• Main Authors: Silva, Zélia, Tong, ZiQiu, Guadalupe Cabral, M., Martins, Catarina, Castro, Rita, Reis, Celso, Trindade, Hélder, Konstantopoulos, Konstantinos, Videira, Paula A.
• Format: Article
• Language: English
• Subjects: Adhesion; Cancer Vaccines - immunology; Cells, Cultured; Dendritic Cells - drug effects; Dendritic Cells - immunology; Humans; IFN-γ; Interferon-gamma - immunology; Interferon-gamma - pharmacology; Monocyte-derived dendritic cells; Monocytes - immunology; Oligosaccharides - immunology; Selectin; Selectins - immunology; Shear flow
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.05.026

► The role of the selectin binding determinant sLex was studied in mo-DCs. ► sLex is required for maximal mo-DC binding to endothelial cells. ► Mo-DCs bind to selectins via a sLex-dependent pathway. ► PSGL-1 is indispensable for P- and L-, but not E-selectin recognition. ► IFN-γ increases sLex expression in mo-DCs, probably by enhancing C2GnT-I synthesis. The limited efficacy of monocyte-derived dendritic cell (mo-DC)-based vaccines is primarily attributed to the reduced mo-DC migratory capacity. One undefined aspect is the initial binding of mo-DCs to endothelial cells and vascular selectins. In this study, we investigated the role and modulation of the selectin binding determinant sialyl Lewisx (sLex) in selectin-dependent mo-DC binding. Our data reveal that sLex is required for maximal binding of mo-DCs to tumor necrosis factor (TNF)-α-activated endothelial cells under static conditions, as evidenced by the use of sialidase. Sialidase treatment also abrogated mo-DC cell tethering to immobilized, purified P-, L-, or E-selectin under flow. The requirement of sLex-dependent binding of mo-DC to selectins was further substantiated by using sLex free sugar and anti-sLex antibody, which significantly suppressed mo-DC-selectin binding. P-selectin glycoprotein ligand-1 is required for mo-DC binding to both P- and L-selectin, but it is dispensable for E-selectin recognition. Interestingly, the extent of mo-DC tethering was maximal on P-selectin, followed by E- and L- selectin. Accordingly, L-selectin mediated faster mo-DC rolling than E- or P-selectin. Interferon (IFN)-γ induces a significant increase in mo-DC surface sLex expression, which is probably due to the enhanced synthesis of C2GnT-I. These findings may contribute to improving mo-DC-based vaccination protocols.