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

Zélia Silva, Zi Qiu Tong, M. Guadalupe Cabral, Catarina Martins, Rita Castro, Celso Reis, Hélder Trindade, Konstantinos Konstantopoulos, Paula A. Videira

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18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)459-464
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume409
Issue number3
DOIs
Publication statusPublished - Jun 10 2011

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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