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Blood, 15 November 2000, Vol. 96, No. 10, pp. 3585-3591
PHAGOCYTES
P-selectin glycoprotein ligand-1 supports rolling on E- and
P-selectin in vivo
Keith E. Norman,
Andreas G. Katopodis,
Gebhard Thoma,
Frank Kolbinger,
Anne E. Hicks,
Matthew J. Cotter,
A. Graham Pockley, and
Paul G. Hellewell
From the Cardiovascular Research Group and Section of
Surgery, Division of Clinical Sciences (NGH), University of Sheffield,
United Kingdom; and Novartis Pharma AG, Transplantation Preclinical
Research, Basel, Switzerland.
Selectin-dependent rolling is the earliest observable event in the
recruitment of leukocytes to inflamed tissues. Several glycoproteins
decorated with sialic acid, fucose, and/or sulfate have been shown to
bind the selectins. The best-characterized selectin ligand is
P-selectin glycoprotein-1 (PSGL-1) that supports P-selectin- dependent
rolling in vitro and in vivo. In vitro studies have suggested that
PSGL-1 may also be a ligand for E- and L-selectins. To study the in
vivo function of PSGL-1, without the influence of other leukocyte
proteins, the authors observed the interaction of PSGL-1-coated
microspheres in mouse venules stimulated to express P- and/or
E-selectin. Microspheres coated with functional recombinant PSGL-1
rolled in surgically stimulated and tumor necrosis factor alpha
(TNF )-stimulated mouse venules. P-selectin deficiency or inhibition
abolished microsphere rolling in surgically and TNF-stimulated venules, whereas E-selectin deficiency or inhibition increased microsphere rolling velocity in TNF-stimulated venules. The results suggest that P-selectin-PSGL-1 interaction alone is sufficient to
mediate rolling in vivo and that E-selectin-PSGL-1 interaction supports slow rolling.
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