Abstract
Abstract
Selectins play a central role in the trafficking of activated T cells by mediating tethering and rolling on vascular endothelium, acting as a beacon to help navigate them to the site of infection. Here we present a comprehensive binding and in vitro functional analysis of E-selectin ligands expressed on human activated T cells. Using a mass-spectrometric approach we identified a number of glycoproteins that may act as physiological E-selectin ligands on human activated T cells and focused on comparing the role the previously identified well-known E-selectin ligands, PSGL-1 (P-selectin glycoprotein ligand 1) to the newly identified ligand CD44. We show that CD44 from human activated CD4+ and CD8+ T cells binds E-selectin, and that immobilized CD44 mediates tethering and rolling of E-selectin expressing CHO cells via sialylated N-linked glycans. By knocking down CD44 and/or PSGL-1 in primary human activated T cells, our data demonstrate for the first time that CD44 is essential for mediating the rolling over E-selectin and thereby cooperates with PSGL-1 as a major E-selectin ligand on human activated T cells. This has major implications in the development of targeted therapies to combat inflammatory diseases and in transplantation settings.
Disclosures
No relevant conflicts of interest to declare.
Original language | English (US) |
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Pages (from-to) | 3429-3429 |
Number of pages | 1 |
Journal | Blood |
Volume | 126 |
Issue number | 23 |
DOIs | |
State | Published - Dec 3 2015 |
Bibliographical note
KAUST Repository Item: Exported on 2021-12-13ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Immunology
- Hematology