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Blood, 15 June 2001, Vol. 97, No. 12, pp. 3812-3819
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Severe impairment of leukocyte rolling in venules of core 2 glucosaminyltransferase-deficient mice
Markus Sperandio,
Aravinda Thatte,
Dan Foy,
Lesley G. Ellies,
Jamey D. Marth, and
Klaus Ley
From the Department of Biomedical Engineering,
University of Virginia, Charlottesville, and the Howard Hughes Medical
Institute, Department of Cellular and Molecular Medicine, University of
California, La Jolla.
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 1-6-N-glucosaminyltransferase (C2GlcNAcT-I) for synthesis of
functional selectin ligands in vivo, leukocyte rolling flux and
velocity were studied in venules of untreated and tumor necrosis
factor- (TNF )-pretreated autoperfused cremaster muscles of
C2GlcNAcT-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 TNF -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 C2GlcNAcT-I dependent.
In addition, E-selectin-mediated rolling in vivo is partially
dependent on the targeted C2GlcNAcT-I.

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