Abstract
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, α(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.
Topics

No keywords indexed for this article. Browse by subject →

References
31
[1]
Curr. Opin. Cell Biol. (2003) 10.1016/j.ceb.2003.08.002
[2]
The role of selectins in inflammation and disease

Klaus Ley

Trends in Molecular Medicine 2003 10.1016/s1471-4914(03)00071-6
[3]
Nature. (1995) 10.1038/373615a0
[4]
J. Immunol. (1997) 10.4049/jimmunol.159.7.3574
[5]
J. Clin. Invest. (1999) 10.1172/jci4705
[6]
J. Cell Biol. (2001) 10.1083/jcb.153.6.1277
[7]
Physiol. Rev. (1999) 10.1152/physrev.1999.79.1.181
[8]
Curr. Opin. Cell Biol. (2002) 10.1016/s0955-0674(02)00367-8
[9]
J. Exp. Med. (1999) 10.1084/jem.190.12.1769
[10]
J. Clin. Invest. (2002) 10.1172/jci0214151
[11]
[12]
Science. (2002) 10.1126/science.1069659
[13]
[14]
[15]
[16]
Immunity. (1994) 10.1016/1074-7613(94)90041-8
[17]
Susceptibility to Infection and Altered Hematopoiesis in Mice Deficient in Both P- and E-Selectins

Paul S Frenette, Tanya N Mayadas, Helen Rayburn et al.

Cell 1996 10.1016/s0092-8674(00)81032-6
[18]
J. Exp. Med. (1996) 10.1084/jem.183.5.2329
[19]
Circ. Res. (1996) 10.1161/01.res.79.6.1196
[20]
Lab. Invest. (1998)
[21]
J. Cell Biol. (1995) 10.1083/jcb.128.4.661
[22]
[23]
[24]
Blood. (2002) 10.1182/blood.v99.1.336
[25]
J. Exp. Med. (1999) 10.1084/jem.189.1.37
[26]
J. Immunol. (2004) 10.4049/jimmunol.172.12.7780
[27]
[28]
J. Clin. Invest. (2002) 10.1172/jci0214047
[29]
Proc. Natl. Acad. Sci. USA. (2002) 10.1073/pnas.052522799
[30]
J. Immunol. (1999) 10.4049/jimmunol.163.9.4917
[31]
CD44: From adhesion molecules to signalling regulators

Helmut Ponta, Larry Sherman, Peter A. Herrlich

Nature Reviews Molecular Cell Biology 2003 10.1038/nrm1004