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Leukocyte rolling in vivo is mediated by P-selectin glycoprotein ligand- 1
KE Norman, KL Moore, RP McEver and K Ley
Department of Biomedical Engineering, University of Virginia Health
Sciences Center, Charlottesville 22908, USA.
Leukocyte rolling, an early and important step in the inflammatory
response, is mediated by the selectin family of adhesion molecules. The
selectins bind with low affinity to sialylated and fucosylated glycans such
as sialyl Lewisx (sLex), but bind with high affinity to only a few specific
glycoproteins on cell surfaces. One such glycoprotein is P- selectin
glycoprotein ligand-1 (PSGL-1). The relative contributions of low- and
high-affinity ligands to leukocyte rolling in vivo are unknown. We show
here that a monoclonal antibody to PSGL-1 (PL1) dramatically reduces
rolling of human polymorphonuclear neutrophils (PMN) and promyelocytic
HL-60 cells in venules of acutely exteriorized rat mesentery. Control PMN
and HL-60 cell rolling flux fractions were 39% +/- 3% and 33% +/- 5%, which
were reduced by PL1 to 7% +/- 2% and 6% +/- 2%, respectively. Similar
reductions were seen with F(ab) fragments of PL1. PL1-treated PMN rolled at
significantly higher mean velocities than untreated PMN owing to
intermittent rather that continuous interactions. These findings show that
interaction of P- selectin with PSGL-1 is required for rolling of myeloid
cells in mesenteric venules at physiologic shear stress in vivo.
Volume 86,
Issue 12,
pp. 4417-4421,
12/15/1995
Copyright © 1995 by The American Society of Hematology
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M.-C. Huang, O. Zollner, T. Moll, P. Maly, A. D. Thall, J. B. Lowe, and D. Vestweber
P-selectin Glycoprotein Ligand-1 and E-selectin Ligand-1 Are Differentially Modified by Fucosyltransferases Fuc-TIV and Fuc-TVII in Mouse Neutrophils
J. Biol. Chem.,
September 29, 2000;
275(40):
31353 - 31360.
[Abstract]
[Full Text]
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M. K. Wild, M.-C. Huang, U. Schulze-Horsel, P. A. van der Merwe, and D. Vestweber
Affinity, Kinetics, and Thermodynamics of E-selectin Binding to E-selectin Ligand-1
J. Biol. Chem.,
August 17, 2001;
276(34):
31602 - 31612.
[Abstract]
[Full Text]
[PDF]
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