E-Selectin (also known as Endothelial Leukocyte Adhesion Molecule-1, ELAM-1, or CD62E) is a 115 kDa, type I transmembrane glycoprotein expressed only on endothelial cells and only after activation by inflammatory cytokines (IL-1β or TNF-α) or endotoxins (1-4). Expression is transitory, reaching a maximum within about 6 hours of stimulation and then declining with shedding of soluble E-Selectin (1-5). Cell-surface E-Selectin is a mediator of the rolling attachment of leukocytes to the endothelium, an essential step in extravasation of leukocytes at the site of inflammation (1-6) thereby playing a key role in localized inflammatory response. E-Selectin is believed to be particularly important in inflammation involving the skin (4).

The extracellular part of E-Selectin includes a calcium-dependent C2-type lectin domain, an epidermal growth factor (EGF) domain, and six repeats of a complement-regulatory-protein-like sequence (1-4). E-Selectin binds sialyl Lewis X (sLex), a sialic acid-galactose-N-acetylglucosamine-fructose tetrasaccharide, but the actual recognition is thought to be for a specific presentation of those glycosyl units in a precise three-dimensional configuration on a specific glycoprotein rather than for that particular carbohydrate (4).

Soluble E-Selectin (sE-Selectin) is found in the blood of healthy individuals (7, 8), probably arising from proteolytic cleavage of the surface-expressed molecule (5, 9). Elevated levels of sE-Selectin in serum have been reported in a variety of pathological conditions (8, 10-14). Although it might be anticipated that sE-Selectin would suppress leukocyte migration by competing with surface-associated E-Selectin, it may actually activate neutrophils and act as a pro-inflammatory agent (15).

Bevilacqua, M.P. and R.M. Nelson (1993) J. Clin. Invest. 91:379.

McEver, R.P. (1994) Curr. Opin. Immunol. 6:75.

Tedder, T.F. et al. (1995) FASEB J. 9:866.

Kansas, G.S. (1996) Blood 88:3259.

Wyble, C.W. et al. (1997) J. Surg. Res. 73:107.

Kunkel, E.J. and K. Ley (1996) Circ. Res. 79:1196.

Lobb, R.R. et al. (1991) J. Immunol. 147:124.

Gearing, A.J.H. et al. (1992) Annals N.Y. Acad. Sci. 667:324.

Morandini, R. et al. (1996) Am. J. Physiol. 270:807.

Hebbar, M. et al. (1998) Clin. Cancer Res. 4:373.

Ohsaka, A. et al. (1998) Br. J. Haematol. 100:66.

Frijns, C.J.M. et al. (1997) Stroke 28:2214.

Okajima, K. et al. (1997) Am. J. Hematol. 54:219.

Matsuura, N. et al. (1997) Anticancer Res. 17:1367.

Ruchaud-Sparagano, M-H. et al. (1998) Eur. J. Immunol. 28:80.