title: Sialyl Lewisx-dependent binding of human monocyte-derived dendritic cells to selectins.
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 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)-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 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)-γ 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.
authors: CEDOC, Departamento de Imunologia, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal.
authors: Zélia
authors: Z
authors: Silva
authors: ZiQiu
authors: Z
authors: Tong
authors: M Guadalupe
authors: MG
authors: Cabral
authors: Catarina
authors: C
authors: Martins
authors: Rita
authors: R
authors: Castro
authors: Celso
authors: C
authors: Reis
authors: Hélder
authors: H
authors: Trindade
authors: Konstantinos
authors: K
authors: Konstantopoulos
authors: Paula A
authors: PA
authors: Videira
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