E-Selectin


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 chemoattractant (Ley 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 m/s (Jung et al., 1998a; Kunkel and Ley, 1996a) and about 15 m/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 2 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.

 

View various information about this molecule at the National Center for Biotechnology Information.

 

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 it into the text box on the BLAST page.
  • Search results will provide a list of homologous molecules and show a statistical relationship between high-scoring segment pairs.
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Read the following categorized abstracts or link to Medline to conduct your own query.

  • Cloning of the human gene: Endothelial leukocyte adhesion molecule-1: An inducible receptor for neutrophils related to complement regulatory proteins and lectins.
  • Cloning of the murine gene: Cloning of the mouse endothelial selectins. Expression of both E- and P-selectin is inducible by tumor necrosis factor.
  • Potential disease relevance: Use of radiolabeled monoclonal antibody against E-selectin for imaging of endothelial activation in rheumatoid arthritis.
  • Microcirculation-based publication: Distinct phenotype of E-selectin deficient mice. E-selectin is required for slow leukocyte rolling in vivo.
  • First knockout mouse: Characterization of E-selectin-deficient mice: demonstration of overlapping function of the endothelial selectins.
  • Other: Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1.

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