E-selectin is expressed on inflamed endothelial cells in response to
treatment with inflammatory cytokines (Bevilacqua
et al., 1989). Intravital microscopic experiments have shown that
its function in mediating leukocyte rolling is largely redundant with
that of P-selectin (Hickey
et al., 1999; Bullard
et al., 1996; Kunkel
and Ley, 1996). Consequently, E-selectin deficient mice have only
a subtle defect in leukocyte rolling as shown by much faster rolling velocities
in these mice (Kunkel
and Ley, 1996). In addition to mediating leukocyte rolling, E-selectin
participates in the conversion of rolling to
firm adhesion. E-selectin deficient mice
have a reduced number of firmly adherent leukocytes in response to local
et al., 1998) or cytokine stimulation (Milstone
et al., 1998). This defect may be related to the more rapid rolling
velocities in the absence of E-selectin. E-selectin is expressed in skin
microvessels under baseline conditions (Keelan
et al., 1994), and there is some evidence that E-selectin is of particular
importance in skin inflammation, because it supports the recruitment of
skin-specific T lymphocytes (Picker
et al., 1991a).
The ligands for E-selectin that is responsible for the rolling interaction
are unknown. Two candidate ligands, PSGL-1 (Asa
et al., 1995; Lenter
et al., 1994) and E-selectin ligand-1 (ESL-1) (Steegmaier
et al., 1995) have not been shown to be required for E-selectin mediated
leukocyte rolling under any condition. It is not clear whether the physiological
ligand for E-selectin is a glycoprotein. Some glycolipids can support
E-selectin dependent rolling in vitro (Alon
et al., 1995a).
E-selectin mediates much slower rolling than P-selectin.
Dependent on the level of expression of E-selectin, rolling velocities
range between less than 5 µm/s (Jung
et al., 1998a; Kunkel
and Ley, 1996a) and about 15 µm/s (Ley
et al., 1998). Since the dissociation rate or off-rate of E-selectin
is very similar to that of P-selectin (Smith
et al., 1999), it is very likely that E-selectin or its ligand or
both are expressed at much higher site densities than P-selectin and PSGL-1.
The velocity of E-selectin mediated rolling is remarkably invariant with
wall shear rate. Based on the finding that E-selectin also participates
in firm adhesion (Ley
et al., 1998), mice deficient for both E-selectin and CD18,
the common beta chain of the Ñ2 integrins were generated. These mice show
a severe inflammatory defect leading to early lethality (Forlow et al.,
1999), suggesting that E-selectin operates "downstream" from P-selectin,
more toward the firm adhesion step of the cascade.
Click for an image of a 3-D
Structure of E-Selectin.
|Search similar protein and nucleotide sequences between various
species using BLAST (Basic Local Alignment Search Tool)
- Copy the desired sequence from the GenBank Database and paste
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Read the following categorized abstracts or link to Medline
to conduct your own query.
of the human gene: Endothelial leukocyte adhesion molecule-1:
An inducible receptor for neutrophils related to complement regulatory
proteins and lectins.
of the murine gene: Cloning of the mouse endothelial selectins.
Expression of both E- and P-selectin is inducible by tumor necrosis
disease relevance: Use of radiolabeled monoclonal antibody
against E-selectin for imaging of endothelial activation in rheumatoid
publication: Distinct phenotype of E-selectin deficient mice.
E-selectin is required for slow leukocyte rolling in vivo.
knockout mouse: Characterization of E-selectin-deficient mice:
demonstration of overlapping function of the endothelial selectins.
Angiogenesis mediated by soluble forms of E-selectin and vascular
cell adhesion molecule-1.
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