Abstract
Leukocyte capture and rolling are mediated by selectins expressed on leukocytes (L-selectin) and the vascular endothelium (P- and E-selectin). To investigate the role of core 2 β1-6-N-glucosaminyl-transferase (C2GIcNAcT-I) for synthesis of functional selectin ligands in vivo, leukocyte rolling flux and velocity were studied in venules of untreated and tumor necrosis factor-α (TNFα)-pretreated autoperfused cremaster muscles of C2GIcNAcT-I-deficient (core 2-/-) and littermate control mice. In untreated core 2-/- mice, leukocyte rolling was dramatically reduced with markedly increased rolling velocities (81 ± 4 μm/s vs 44 ± 3 μm/s). The reduced rolling in core 2-/- mice was due mainly to severely impaired binding of P-selectin to P-selectin glycoprotein ligand-1 (PSGL-1). Some rolling remained after blocking PSGL-1 in controls but not in core 2-/- mice. In TNFα-pretreated mice, rolling was markedly reduced in core 2-/- mice owing to impaired P-selectin- and E-selectin-mediated rolling. Rolling velocities in core 2-/- mice treated with an E-selectin-blocking monoclonal antibody (59 ± 4 μm/s) were significantly higher than in controls (14 ± 1 μm/s), which provides further evidence for the severe impairment in P-selectin-mediated rolling. In conclusion, P-selectin ligands including PSGL-1 are largely C2GIcNAcT-I dependent. In addition, E-selectin-mediated rolling in vivo is partially dependent on the targeted C2GIcNAcT-I.
Original language | English (US) |
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Pages (from-to) | 3812-3819 |
Number of pages | 8 |
Journal | Blood |
Volume | 97 |
Issue number | 12 |
DOIs | |
State | Published - Jun 15 2001 |
Externally published | Yes |
ASJC Scopus subject areas
- Biochemistry
- Immunology
- Hematology
- Cell Biology