The Journal of Experimental Medicine
StemCell Technologies
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Published online 11 April 2005 doi:10.1084/jem.20042014
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 8, 1183-1189
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BRIEF DEFINITIVE REPORT

 CD44 is a physiological E-selectin ligand on neutrophils

Yoshio Katayama, Andrés Hidalgo, Jungshan Chang, Anna Peired, and Paul S. Frenette

Department of Medicine and Center for Immunobiology, Mount Sinai School of Medicine, New York, NY 10029

CORRESPONDENCE Paul Frenette: paul.frenette{at}mssm.edu

The selectin family of adhesion molecules and their glycoconjugated ligands are essential for blood polymorphonuclear neutrophil (PMN) extravasation into inflammatory and infectious sites. However, E-selectin ligands on PMNs are not well characterized. We show here that CD44 immunopurified from G-CSF–differentiated 32D cells or from peripheral blood PMNs binds specifically to E-selectin. In contrast, CD44 extracted from bone marrow stromal or brain endothelial cell lines does not interact with E-selectin, suggesting cell-specific posttranslational modifications of CD44. PMN-derived CD44 binding activity is mediated by sialylated, {alpha}(1,3) fucosylated, N-linked glycans. CD44 enables slow leukocyte rolling on E-selectin expressed on inflamed endothelium in vivo and cooperates with P-selectin glycoprotein ligand–1 to recruit neutrophils into thioglycollate-induced peritonitis and staphylococcal enterotoxin A–injected skin pouch. CD44 extracted from human PMNs also binds to E-selectin. Moreover, we demonstrate that CD44 is hypofucosylated in PMNs from a patient with leukocyte adhesion deficiency type II, suggesting that it contributes to the syndrome. These findings thus suggest broader roles for CD44 in the innate immune response and uncover a potential new target for diseases in which selectins play a prominent role.

Abbreviations used: DKO, double knockout; ESL, E-selectin ligand; FucT, fucosyltransferase; HA, hyaluronic acid; LADII, leukocyte adhesion deficiency type II; OSGE, O-sialoglycoprotein endopeptidase; PB, peripheral blood; PMN, polymorphonuclear neutrophil; PSGL1; P-selectin glycoprotein ligand-1; SEA, staphylococcal enterotoxin A.

Y. Katayama, A. Hidalgo, and J. Chang contributed equally to this work.

Y. Katayama's present address is Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.


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