TY - JOUR
T1 - Glycolipids support E-selectin-specific strong cell tethering under flow
AU - Burdick, Monica M.
AU - Bochner, Bruce S.
AU - Collins, Brian E.
AU - Schnaar, Ronald L.
AU - Konstantopoulos, Konstantinos
N1 - Funding Information:
This work was supported by a Whitaker Foundation Grant, National Institutes of Health Grant AI45115, National Science Foundation Grant BES 9978160, and a National Science Foundation Graduate Research Fellowship (to M.M.B). 1Current address: The Scripps Research Institute, La Jolla, CA. 2To whom correspondence should be addressed at Department of Chemical Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218-2694. Fax: (410) 516-5510. E-mail: konst_k@jhu.edu.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - This study provides functional evidence that glycosphingolipids constitute ligands for E-selectin but not P-selectin. Chinese hamster ovary (CHO) cells expressing E-selectin (CHO-E) or P-selectin (CHO-P) were perfused over α2,3-sialyl Lewis X (α2,3-sLex) presented as the hexaosylceramide glycosphingolipid adsorbed in a monolayer containing phosphatidylcholine and cholesterol. CHO-E cells tethered extensively and formed slow, stable rolling interactions with α2,3-sLex glycosphingolipid but not with the comparable α2,6-sLex glycosphingolipid. Tethering/rolling varied with wall shear stress, selectin density, and ligand density. In contrast, α2,3-sLex glycosphingolipid supported only limited, fast CHO-P cell rolling. As calculated from a stochastic model of cell rolling, the step size between successive bond releases from the α2,3-sLex glycosphingolipid was smaller for CHO-E than CHO-P cells, whereas the opposite effect was observed for the waiting time between these events. Detachment assays revealed stronger adhesive interactions of CHO-E than CHO-P cells with α2,3-sLex glycosphingolipid. These findings indicate that glycosphingolipids expressing an appropriate oligosaccharide mediate cell tethering/rolling via E-selectin but not P-selectin.
AB - This study provides functional evidence that glycosphingolipids constitute ligands for E-selectin but not P-selectin. Chinese hamster ovary (CHO) cells expressing E-selectin (CHO-E) or P-selectin (CHO-P) were perfused over α2,3-sialyl Lewis X (α2,3-sLex) presented as the hexaosylceramide glycosphingolipid adsorbed in a monolayer containing phosphatidylcholine and cholesterol. CHO-E cells tethered extensively and formed slow, stable rolling interactions with α2,3-sLex glycosphingolipid but not with the comparable α2,6-sLex glycosphingolipid. Tethering/rolling varied with wall shear stress, selectin density, and ligand density. In contrast, α2,3-sLex glycosphingolipid supported only limited, fast CHO-P cell rolling. As calculated from a stochastic model of cell rolling, the step size between successive bond releases from the α2,3-sLex glycosphingolipid was smaller for CHO-E than CHO-P cells, whereas the opposite effect was observed for the waiting time between these events. Detachment assays revealed stronger adhesive interactions of CHO-E than CHO-P cells with α2,3-sLex glycosphingolipid. These findings indicate that glycosphingolipids expressing an appropriate oligosaccharide mediate cell tethering/rolling via E-selectin but not P-selectin.
KW - Selectins
KW - Shear
KW - Sialyl Lewis
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U2 - 10.1006/bbrc.2001.4899
DO - 10.1006/bbrc.2001.4899
M3 - Article
C2 - 11374868
AN - SCOPUS:0034808842
SN - 0006-291X
VL - 284
SP - 42
EP - 49
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -