PMID- 21596017 OWN - NLM STAT- MEDLINE DCOM- 20110815 LR - 20211020 IS - 1090-2104 (Electronic) IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 409 IP - 3 DP - 2011 Jun 10 TI - Sialyl Lewisx-dependent binding of human monocyte-derived dendritic cells to selectins. PG - 459-64 LID - 10.1016/j.bbrc.2011.05.026 [doi] AB - 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 Lewis(x) (sLe(x)) in selectin-dependent mo-DC binding. Our data reveal that sLe(x) is required for maximal binding of mo-DCs to tumor necrosis factor (TNF)-alpha-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 sLe(x)-dependent binding of mo-DC to selectins was further substantiated by using sLe(x) free sugar and anti-sLe(x) 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)-gamma induces a significant increase in mo-DC surface sLe(x) expression, which is probably due to the enhanced synthesis of C2GnT-I. These findings may contribute to improving mo-DC-based vaccination protocols. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Silva, Zelia AU - Silva Z AD - CEDOC, Departamento de Imunologia, Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisboa, Portugal. FAU - Tong, ZiQiu AU - Tong Z FAU - Cabral, M Guadalupe AU - Cabral MG FAU - Martins, Catarina AU - Martins C FAU - Castro, Rita AU - Castro R FAU - Reis, Celso AU - Reis C FAU - Trindade, Helder AU - Trindade H FAU - Konstantopoulos, Konstantinos AU - Konstantopoulos K FAU - Videira, Paula A AU - Videira PA LA - eng GR - R01 CA101135/CA/NCI NIH HHS/United States GR - R01 CA101135-08/CA/NCI NIH HHS/United States GR - U54 CA143868/CA/NCI NIH HHS/United States GR - U54 CA143868-02/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110508 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Cancer Vaccines) RN - 0 (Oligosaccharides) RN - 0 (Selectins) RN - 0 (Sialyl Lewis X Antigen) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Cancer Vaccines/immunology MH - Cells, Cultured MH - Dendritic Cells/drug effects/*immunology MH - Humans MH - Interferon-gamma/*immunology/pharmacology MH - Monocytes/immunology MH - Oligosaccharides/*immunology MH - Selectins/*immunology MH - Sialyl Lewis X Antigen PMC - PMC3257975 MID - NIHMS300203 EDAT- 2011/05/21 06:00 MHDA- 2011/08/16 06:00 PMCR- 2012/06/10 CRDT- 2011/05/21 06:00 PHST- 2011/04/28 00:00 [received] PHST- 2011/05/03 00:00 [accepted] PHST- 2011/05/21 06:00 [entrez] PHST- 2011/05/21 06:00 [pubmed] PHST- 2011/08/16 06:00 [medline] PHST- 2012/06/10 00:00 [pmc-release] AID - S0006-291X(11)00779-0 [pii] AID - 10.1016/j.bbrc.2011.05.026 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2011 Jun 10;409(3):459-64. doi: 10.1016/j.bbrc.2011.05.026. Epub 2011 May 8.