TY - JOUR
T1 - Sialyl Lewisx-dependent binding of human monocyte-derived dendritic cells to selectins
AU - Silva, Zélia
AU - Tong, Zi Qiu
AU - Guadalupe Cabral, M.
AU - Martins, Catarina
AU - Castro, Rita
AU - Reis, Celso
AU - Trindade, Hélder
AU - Konstantopoulos, Konstantinos
AU - Videira, Paula A.
N1 - Funding Information:
This study was supported in part by the Fundação para a Ciência e Tecnologia, Portugal – PTDC/SAU-MII/67561/2006 and SFRH/BPD/41168/2007 (Z.S.) and the NIH / NCI R01 CA101135 and U54 CA143868 (K.K.). We thank Sérgio Dias (CEDOC/FCM, IPO, Lisbon) for kind gift of HUVEC and Dário Ligeiro (CHSUL, Lisbon) for the microscopy image acquisition.
PY - 2011/6/10
Y1 - 2011/6/10
N2 - 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.
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 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.
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U2 - 10.1016/j.bbrc.2011.05.026
DO - 10.1016/j.bbrc.2011.05.026
M3 - Article
C2 - 21596017
AN - SCOPUS:80051577888
SN - 0006-291X
VL - 409
SP - 459
EP - 464
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -