E-selectins

Frequently, the EAR is followed by a late phase response 4-6 h later and it is caused by the pulmonary sequestration of eosinophils, neutrophils, mast cells, and T-lymphocytes. This leukocyte recruitment depends on mast cell-derived mediators such as TNFa and various chemokines, as well as on the expression of adhesion molecules on leukocytes (e.g. VLA-4, CD11/18) and vascular endothelial cells (e.g. VCAM-1, ICAM-1, E-selectin). Products of these leukocytes have several functions First, they cause the second phase of bron-choconstriction, mucus secretion, and airway swelling second, they cause tissue destruction third, they launch and entertain the chronic inflammation. 

CD163 (Scavenger receptor) Adhesion molecules (ICAM-1, E-selectin)... 

Figure 47-10. Schematic diagram of the structure of human L-selectin. The extracellular portion contains an amino terminal domain homologous to C-type lectins and an adjacent epidermal growth factor-like domain. These are followed by a variable number of complement regulatory-like modules (numbered circles) and a transmembrane sequence (blackdiamond). A short cytoplasmic sequence (open rectangle) is at the carboxyl terminal. The structures of P- and E-selectin are similar to that shown except that they contain more complement-regulatory modules.The numbers of amino acids in L-, P-, and E- selectins, as deduced from the cDNA sequences, are 385,789, and 589, respectively. (Reproduced, with permission, from Bevilacqua MP, Nelson RM Selectins. J Clin Invest 1993 91 370.)...

Oxidatively modified LDL up-regulates the surfece expression of VCAM-1 and intracellular adhesion molecule-1 (ICAM-1) in cultured endothelial cells, promoting the interactions between both cell types (Kume et al., 1992). This may play a pivotal role in the development of atherosclerosis by promoting the penetration of circulating monocytes into the suben-dothelial space whilst inhibiting the mobility of resident macrophages. It has been previously demonstrated that ICAM-1, E-selectin, and VCAM-1 are up-regulated in the microvasculature of rheumatoid but not control synovium (Corkill et al., 1991 Koch et al., 1991). The association between ox-LDL and increased expression of adhesion molecules in the inflamed synovium has yet to be studied. 

EPA Eicosapentaenoic acid EpDIF Epithelial-derived inhibitory factor also known as epithelium/derived relaxant fector EPO Eosinophil peroxidase EPOR Erythropoietin receptor EPR Effector cell protease EPX Eosinophil protein X ER Endoplasmic reticulum ERCP Endoscopic retrograde cholangiopancreatography E-selectin Endothelial selectin formerly known as endothelial leucocyte adhesion molecule-1 (ELAM-1)... 

D30. Drake, T. A., Cheng, J., Chang, A. C., and Taylor, F. B., Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal Escherichia coli sepsis. Am. J. Pathol. 142, 1458-1470(1993). 

R2. Rainger, E. S., Wautier, M. P., Nash, G. B., and Wautier, J. L., Prolonged E-selectin induction by monocytes potentiates the adhesion of flowing neutrophil to cultured endothelial cells. Br. J. Haematol. 92,192-199 (1996). 

Bennett, B.L., Cruz, R., Lacson, R.G. and Manning, A.M. (1997) Interleukin-4 suppression of tumor necrosis factor alpha-stimulated E-selectin gene transcription is mediated by STAT6 antagonism of NF-kappaB. Journal of Biological Chemistry 272, 10212-10219. 

Haraldsen, G., Kvale, D., Lien, B., Farstad, I.N. and Brandtzaeg, P. (1996) Cytokine-regulated expression of E-selectin, intercellular adhesion molecule-1 (IGAM-1), and vascular cell adhesion molecule-1 (VGAM-1) in human microvascular endothelial cells. Journal of Immunology 156, 2558-2565. 

Hwang SJ, Ballantyne CM, Sharrett AR, Smith LC, Davis CE, Gotto AM Jr, Boerwinkle E (1997) Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases the Atherosclerosis Risk In Communities (ARIC) study. Circulation 96 4219-4225... 

A Compound P-selectin (IC50 mM) L-selectin (IC50 mM) E-selectin (IC50 mM)... 

Parallel synthesis of 62 different fucosylated tripeptides resulted in two ligands with submicromolar affinity for the P-selectin however, the desired activity for the E-selectin was not observed.98 For the E-selectin selectivity, it was necessary to incorporate a hydroxyl group that mimics the 4-hydroxyl of the central Gal in SLex in addition to a Fuc-residue and a carboxylate to obtain ligands with > 10-fold increased activity over that of the SLex tetrasaccharide.81 One of the best ligands was obtained from Thr(a-Fuc)-OEt, which was first /V-acylated with a hydroxyl amino acid and then elongated with a di-acid to furnish the acid mimic of the sialic acid carboxylate (Fig. 14.4). This approach was further developed as a solid-phase method where the molecule was linked to a solid support through the invariable fucosyl moiety.99... 

On the neutrophil, the major selectin expressed is L-selectin. This molecule is constitutively expressed on mature neutrophils but may be expressed at low levels (50% of adult) in neonates. Stimulation of endothelial cells with thrombin, histamine, IL-1 and some other agents induces neutrophils (and other leukocytes) to leave the circulation and adhere to the endothelium. They do this by rolling onto the surface of the endothelium, to which they attach via P-selectin translocated from storage sites in Weibel-Palade bodies to the surface of the endothelium upon activation. The expression of P-selectin is short-lived and is replaced on the endothelial surface by E-selectin (whose expression is also regulated by some cytokines), which continues the endothelial-leukocyte interaction. 

Masamune, A., Igarashi, Y. and Hakomori, S.. 1996, Regulatory role of ceramide in interleukin (IL)-1 -induced E-selectin expression in human umbilical vein endothehal cells. Ceramide errhances IL-1 action, but is not sufficient for E-selectin expression. J. 

Kessner S, Krause A, Rothe U, Bendas G. Investigation of the cellular uptake of E-selectin-targeted immunoliposomes by activated human endothelial cells. Biochim Biophys Acta 2001 1514(2) 177-190. 

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