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transcriptional, fang, yang, plague, relationships, myocardial, leu125val, patients, 22336504, 1110, zhonghua, xin, xue, guan, bing, zhi, komatsu, nagano, sugiura, hagiwara, tanigawa, abiko, 22508864, 3416463, 1128, iai, 06098, 2570, infection, chen, duan, medicinal, ingredients, secretion, txb2, rat, 207481204, 19874221, 08923970902814129, 550, immunopharmacology, immunotoxicology, visser, polyneuropathy, myopathy, features, factors, 7557453, 17038033, 1468, 1331, 01498, 1203, european, neurology, spanaus, 19779041, 186585, 4583, ccl5, promotes, through, mai, guo, 24818768, 4109393, jconrel, 057, 187, controlled, targeted, www, businesswire, com, glycomimetics, announces, plans, initiate, trial, evaluate, gmi, 1359, winkler, barbier, nowlan, jacobsen, forristal, patton, regulates, hematopoietic, stem, dormancy, self, renewal, chemoresistance, 5593456, 23086476, 2969, 1651, price, burness, sivan, warner, cheng, lee, 2016, 340ra73, 31317455, 27225183, 8722465, scitranslmed, aad4059, translational, dormant, micrometastases, reside, niches, regulate, transit, taverna, moher, crowley, hynes, 14718670, 321755, 0307289101, 2004pnas, 763t, 763, null, beta5, 21209777, 2990482, s12307, 010, 0043, mediators, sipkins, runnels, côté, means, june, 7044, 15959517, 2570168, nature03703, 2005natur, 969s, 969, imaging, specialized, microdomains, tumour, engraftment, kang, 24140083, 3947254, pharmthera, 006, pharmacology, stromal, barthel, hays, yazawa, opperman, walley, 23149920, 3548951, 3264, 942, definition, determinants, laferrière, houle, carcinoma, sequential, involving, beta4, 22354589, 15387376, 1023, clin, 0000037708, 09420, lechpammer, long, woodward, kutok, 11632075, 15289332, 0691, 5261, sawada, tsuboi, fukuda, 7507108, 42275, 1425, differential, sublines, exhibiting, potentials, khatib, kontogiannea, fallavollita, jamison, meterissian, brodt, liver, 10096570, 1356, walz, aruffo, kolanus, seed, 1990, lex, determinant, 4984, 1990sci, 1132w, 1132, pober, mendrick, gimbrone, 1987, 2827173, 299728, 1987pnas, 9238b, inducible, 8th, edition, innate, chapter, aoki, laroy, fierro, hudson, 18579791, 2572800, 149641, 3744, henson, schnaar, 21329670, 061, 2011bbrc, 423s, 423, reynolds, e44529, 22970241, 3435295, 0044529, 744529s, mac, novel, delgadillo, cuckler, tees, benencia, 2015, c68, 25339657, 4281670, 00094, 308, isoforms, conditions, gout, tremblay, organ, selectivity, 11272581, 17891461, s10585, 007, 9096, descheny, trujillo, nguyen, 15994950, 1472661, 4653, 5750, kannagi, izawa, koike, miyazaki, kimura, 27761640, 15132763, 11159147, 1349, 7006, tb03219, 377, angiogenesis, zou, shinde, patil, dagia, smith, wargo, interliggi, c415, 15814589, 00289, kumar, philadelphia, saunders, 7216, 7335, pathologic, andrade, toloi, april, effects, soy, bean, huvec, 29123853, 22066752, 13697137, 582970, climacteric, e31874, 22384091, 3286450, 0031874, 731874h, modulation, eniola, adefeso, leeuwenberg, smeets, neefjes, shaffer, cinek, jeunhomme, 1992, 1283598, 1421640, 543, immunology, intercellular, new, york, garland, 8153, 4101, health, esko, freeze, stanley, bertozzi, hart, etzler, eds, 2nd, plainview, cold, spring, harbor, laboratory, press, 978, 87969, 770, essentials, glycobiology, somers, tang, shaw, camphausen, october, 12719907, 11081633, s0092, 8674, 00138, 467, insights, revealed, graves, crowther, chandran, rumberger, 6463, 4338500, 7509040, 367532a0, 1994natur, 532g, 532, williams, johnston, eddy, 1991, 1703529, 52267, 2466, chromosomal, grcm38, grch38, emerging, some, cancers, recurrences, formation, rupture, promoting, weakening, artery, walls, smoking, highly, enhanced, likelihood, inducing, dysfunction, upregulated, exposure, addictive, tobacco, regulated, increase, transcription, therefore, rrd, target, benefit, cigarette, csrc, arr1, nachrs, immunohistochemical, expressions, significantly, plaques, group, especially, neovascular, positively, density, reaction, plaque, associated, intima, study, umbilical, vein, increases, antibody, suppressed, lacking, had, reduced, deficient, selecin, suggest, host, trigger, exocytosis, fimbriae, ompa, cases, elevated, glucose, sepsis, normal, leads, swelling, linings, muscle, restricted, supply, underlying, pathology, cause, symptomatic, cipnm, traditional, medicines, downregulate, berberine, edema, beyond, direct, locally, enables, conjugated, nanoparticles, thioaptamers, containing, anti, payloads, addition, recruit, tumors, pro, enabling, trafficking, hold, promise, future, car, numerous, pieces, evidence, continue, support, minimally, affects, immediately, following, injection, genetic, deletion, furthermore, paradox, recently, trio, showing, constitutively, where, thought, perform, functions, vital, hijacked, specifically, metastasizing, supports, ongoing, efforts, complexity, discrepant, least, substrates, glycan, esl1, combinations, thereof, result, mechanisms, glg1, hematopoiesis, discovered, monocytic, hl60, led, induce, distant, would, enable, arrest, extravasate, form, since, correlates, increasing, multiple, normally, further, mechanistic, cascade, wherein, rates, velcro, allowing, engage, tight, circulating, similar, minutes, rather, produced, demand, progresses, injured, enter, activate, now, tightly, begin, making, way, chemokines, local, macrophages, over, nearby, expressing, correct, will, low, causing, internal, temporary, made, broken, recruiting, glycosphingolipid, neuacα2, glcnacβ1, 2galβ1, 4glcβcer, closely, dr3, mac2, cd44v, lamp2, lamp1, poorly, remains, firmly, demonstrated, detected, surfaces, tropism, both, should, bear, order, surrounding, counter, tyrosine, fgf, glycoreceptor, raising, possibility, initiating, include, members, families, granulocytes, recognizes, binds, sialylated, certain, eosinophils, memory, effector, association, thus, implicating, natural, killer, plant, compounds, estrogen, mixture, reduce, culture, supernatant, daidzein, biochanin, formononetin, genistein, affect, laminar, enhances, naïve, conditioned, setting, conferring, down, protect, reperfusion, forces, vesicles, called, transcribed, translated, transported, production, turn, takes, maximal, occurs, around, returns, baseline, weibel, palade, bodies, repeats, separate, whereas, cytosolic, derives, flanks, cassette, epidermal, repeat, units, intracellular, cytoplasmic, tail, cyto, three, dimensional, determined, resolution, reveals, limited, coordination, predicted, lectins, analysis, indicates, amino, side, chains, neunacα2, glcnac, tetrasaccharide, sushi, terminal, known, cd62, member, ucsc, np_035475, np_000441, nm_011345, nm_000450, mrna, q00690, p16581, uniprot, 20339, 6401, entrez, species, oma, ncbi, databases, orthologs, quickgo, amigo, actin, filament, based, internalization, heterophilic, via, extracellular, space, clathrin, coated, pit, raft, caveola, perinuclear, cytoplasm, cortical, cytoskeleton, cellular, metal, ion, sialic, oligosaccharide, ontology, biogps, lip, atrioventricular, ileal, semi, lunar, 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bp 1 end 169 764 705 bp 1 gene location mouse chr chromosome 1 mouse 2 band 1 h2 2 1 71 35 cm start 163 875 803 bp 2 end 163 885 246 bp 2 rna expression pattern bgee human mouse ortholog top expressed in vena cava left uterine tube testicle seminal vesicula olfactory zone of nasal mucosa trachea gastric mucosa cartilage tissue mucosa of urinary bladder gallbladder top expressed in transitional epithelium of urinary bladder spermatid spermatocyte granulocyte endothelial cell of lymphatic vessel intestinal villus semi lunar valve ileal epithelium atrioventricular valve lip more reference expression data biogps more reference expression data gene ontology molecular function phospholipase binding oligosaccharide binding protein binding transmembrane signaling receptor activity carbohydrate binding sialic acid binding metal ion binding cellular component integral component of membrane membrane cortical cytoskeleton plasma membrane perinuclear region of cytoplasm caveola membrane raft clathrin coated pit extracellular space integral component of plasma membrane biological process leukocyte cell cell adhesion heterophilic cell cell adhesion via plasma membrane cell adhesion molecules response to interleukin 1 positive regulation of receptor internalization actin filament based process leukocyte migration involved in inflammatory response activation of phospholipase c activity response to tumor necrosis factor response to lipopolysaccharide cell adhesion regulation of inflammatory response leukocyte tethering or rolling inflammatory response leukocyte migration calcium mediated signaling sources amigo quickgo orthologs databases ncbi entry oma entry species human mouse entrez 6401 20339 ensembl ensg00000007908 ensmusg00000026582 uniprot p16581 q00690 refseq mrna nm_000450 nm_011345 refseq protein np_000441 np_035475 location ucsc chr 1 169 72 169 76 mb chr 1 163 88 163 89 mb pubmed search 3 4 wikidata view edit human view edit mouse e selectin also known as cd62 antigen like family member e cd62e endothelial leukocyte adhesion molecule 1 elam 1 or leukocyte endothelial cell adhesion molecule 2 lecam2 is a selectin cell adhesion molecule expressed only on endothelial cells activated by cytokines like other selectins it plays an important part in inflammation in humans e selectin is encoded by the sele gene 5 structure edit e selectin has a cassette structure an n terminal c type lectin domain an egf epidermal growth factor like domain 6 sushi domain scr repeat units a transmembrane domain tm and an intracellular cytoplasmic tail cyto the three dimensional structure of the ligand binding region of human e selectin has been determined at 2 0 å resolution in 1994 6 the structure reveals limited contact between the two domains and a coordination of ca 2 not predicted from other c type lectins structure function analysis indicates a defined region and specific amino acid side chains that may be involved in ligand binding the e selectin bound to sialyl lewis x sle x neunacα2 3galβ1 4 fucα1 3 glcnac tetrasaccharide was solved in 2000 7 gene and regulation edit in humans e selectin is encoded by the sele gene its c type lectin domain egf like scr repeats and transmembrane domains are each encoded by separate exons whereas the e selectin cytosolic domain derives from two exons the e selectin locus flanks the l selectin locus on chromosome 1 8 different from p selectin which is stored in vesicles called weibel palade bodies e selectin is not stored in the cell and has to be transcribed translated and transported to the cell surface the production of e selectin is stimulated by the expression of p selectin which in turn is stimulated by tumor necrosis factor α tnfα interleukin 1 il 1 and lipopolysaccharide lps 9 10 it takes about two hours after cytokine recognition for e selectin to be expressed on the endothelial cell s surface maximal expression of e selectin occurs around 6 12 hours after cytokine stimulation and levels returns to baseline within 24 hours 10 shear forces are also found to affect e selectin expression a high laminar shear enhances acute endothelial cell response to interleukin 1β in naïve or shear conditioned endothelial cells as may be found in the pathological setting of ischemia reperfusion injury while conferring rapid e selectin down regulation to protect against chronic inflammation 11 phytoestrogens plant compounds with estrogen like biological activity such as genistein formononetin biochanin a and daidzein as well as a mixture of these phytoestrogens were found able to reduce e selectin as well as vcam 1 and icam 1 on cell surface and in culture supernatant 12 ligands edit e selectin recognizes and binds to sialylated carbohydrates present on the surface proteins of certain leukocytes e selectin ligands are expressed by neutrophils monocytes eosinophils memory effector t like lymphocytes and natural killer cells each of these cell types is found in acute and chronic inflammatory sites in association with expression of e selectin thus implicating e selectin in the recruitment of these cells to such inflammatory sites these carbohydrates include members of the lewis x and lewis a families found on monocytes granulocytes and t lymphocytes 13 the glycoprotein esl 1 present on neutrophils and myeloid cells was the first counter receptor for e selectin to be described it is a variant of the tyrosine kinase fgf glycoreceptor raising the possibility that its binding to e selectin is involved in initiating signaling in the bound cells p selectin glycoprotein ligand 1 psgl 1 derived from human neutrophils is also a high efficiency ligand for endothelium expressed e selectin under flow 14 it mediates the rolling of leukocytes on the activated endothelium surrounding an inflamed tissue both esl 1 and psgl 1 should bear sialyl lewis a x in order to bind e p selectins 15 e selectin is found to mediate the adhesion of tumor cells to endothelial cells by binding to e selectin ligands on the tumor cells e selectin ligands also play a role in cancer metastasis the role of these two e selectin ligands in metastasis in vivo is poorly defined and remains to be firmly demonstrated psgl 1 was detected on the surfaces of bone metastatic prostate tumor cells suggesting that it may have a functional role in the bone tropism of prostate tumor cells 16 in cancer cells cd44 death receptor 3 dr3 lamp1 and lamp2 were identified as e selectin ligands present on colon cancer cells 17 and cd44v mac2 bp and gangliosides were identified as e selectin ligands present on breast cancer cells 18 19 20 on human neutrophils the glycosphingolipid neuacα2 3galβ1 4glcnacβ1 3 galβ1 4 fucα1 3 glcnacβ1 3 2 galβ1 4glcnacβ1 3 2galβ1 4glcβcer and closely related structures are functional e selectin receptors 21 function edit role in inflammation edit during inflammation e selectin plays an important part in recruiting leukocytes to the site of injury the local release of cytokines il 1 and tnf α by macrophages in the inflamed tissue induces the over expression of e selectin on endothelial cells of nearby blood vessels 22 leukocytes in the blood expressing the correct ligand will bind with low affinity to e selectin also under the shear stress of blood flow causing the leukocytes to roll along the internal surface of the blood vessel as temporary interactions are made and broken as the inflammatory response progresses chemokines released by injured tissue enter the blood vessels and activate the rolling leukocytes which are now able to tightly bind to the endothelial surface and begin making their way into the tissue 13 p selectin has a similar function but is expressed on the endothelial cell surface within minutes as it is stored within the cell rather than produced on demand 13 role in cancer edit e selectin was first discovered as an transmembrane receptor induced in endothelial cells upon inflammatory stimulation which mediated adhesion of monocytic or hl60 leukemic cells 23 24 this led to the hypothesis that cancer cells secreted inflammatory cytokines such as il 1β or tnfα to induce e selectin at distant metastatic sites this induction would enable circulating tumor cells to arrest at stimulated sites roll along activated endothelium extravasate and form metastases 25 studies since have shown that e selectin binding to colon cancer cells correlates with increasing metastatic potential 26 and that cancer cells of multiple tumor types bind e selectin using glycoprotein or glycolipid ligands normally expressed on immune cells 27 28 studies have further described a mechanistic cascade wherein cancer cells first bind e selectin at shear flow rates e selectin binding results in a velcro like interaction allowing the cancer cells to engage higher affinity integrin binding that eventually results in a tight binding between tumor cells and the activated endothelium 29 30 while numerous pieces of in vitro and clinical evidence continue to support this hypothesis of e selectin mediated cancer metastasis in vivo studies of cancer metastasis have shown that e selectin knockout only minimally affects leukemic cell adhesion to bone immediately following injection 31 while experimental lung metastasis is not affected by the genetic deletion of e selectin 32 33 furthermore studies have also shown that primary tumor growth is increased in e selectin knockout mice 34 35 this paradox was more recently solved by a trio of studies showing that e selectin is only constitutively expressed in the bone marrow endothelium 36 where it is thought to perform functions vital to hematopoiesis 37 that are hijacked specifically by cells metastasizing to bone and not other sites 38 this data supports ongoing clinical efforts to inhibit breast cancer bone metastasis with e selectin blocking agents 39 the complexity of e selectin ligand biology may also play a role in these discrepant in vitro and in vivo results at least 15 different glycoprotein and glycolipid substrates for e selectin have been described on various cancer cells while only n glycan glg1 esl1 was shown to mediate bone metastasis 40 other ligands or combinations thereof may result in distinct mechanisms during cancer metastasis beyond a direct interaction with tumor cells e selectin induction in response to cytokines locally secreted by cancer cells enables specific tumor targeting of slex conjugated nanoparticles or thioaptamers containing anti tumor payloads 41 in addition e selectin may also function to recruit monocytes to primary tumors or lung metastases to promote an inflammatory pro tumor microenvironment 42 blocking these interactions or enabling trafficking of car t cells to e selectin positive sites may hold promise for future therapeutic development pathological relevance edit critical illness polyneuromyopathy edit in cases of elevated blood glucose levels such as in sepsis e selectin expression is higher than normal resulting in greater microvascular permeability the greater permeability leads to edema swelling of the skeletal endothelium blood vessel linings resulting in skeletal muscle ischemia restricted blood supply and eventually necrosis cell death this underlying pathology is the cause of the symptomatic disease critical illness polyneuromyopathy cipnm 43 traditional chinese herbal medicines like berberine downregulate e selectin 44 pathogen attachment edit study shows the adherence of porphyromonas gingivalis to human umbilical vein endothelial cells increases with the induction of e selectin expression by tnf α an antibody to e selectin and sialyl lewis x suppressed p gingivalis adherence to stimulated huvecs p gingivalis mutants lacking ompa like proteins pgm6 7 had reduced adherence to stimulated huvecs but fimbriae deficient mutants were not affected e selecin mediated p gingivalis adherence activated endothelial exocytosis these results suggest that the interaction between host e selectin and pathogen pgm6 7 mediates p gingivalis adherence to endothelial cells and may trigger vascular inflammation 45 acute coronary syndrome edit the immunohistochemical expressions of e selectin and pecam 1 were significantly increased at intima in vulnerable plaques of acute coronary syndrome acs group especially in neovascular endothelial cells and positively correlated with inflammatory cell density suggesting that pecam 1 and e selectin might play an important role in inflammatory reaction and development of vulnerable plaque e selectin ser128arg polymorphism is associated with acs and it might be a risk factor for acs 46 nicotine mediated induction edit smoking is highly correlated with enhanced likelihood of atherosclerosis by inducing endothelial dysfunction in endothelial cells various cell adhesion molecules including e selectin are shown to be upregulated upon exposure to nicotine the addictive component of tobacco smoke nicotine stimulated adhesion of monocytes to endothelial cells is dependent on the activation of α7 nachrs β arr1 and csrc regulated increase in e2f1 mediated transcription of e selectin gene therefore agents such as rrd 251 that can target activity of e2f1 may have potential therapeutic benefit against cigarette smoke induced atherosclerosis 47 cerebral aneurysm edit it s also found that e selectin expression increased in human ruptured cerebral aneurysm tissues e selectin might be an important factor involved in the process of cerebral aneurysm formation and rupture by promoting inflammation and weakening cerebral artery walls 48 as a biomarker edit e selectin is also an emerging biomarker for the metastatic potential of some cancers including colorectal cancer and recurrences 49 references edit 1 2 3 grch38 ensembl release 89 ensg00000007908 ensembl may 2017 1 2 3 grcm38 ensembl release 89 ensmusg00000026582 ensembl may 2017 human pubmed reference national center for biotechnology information u s national library of medicine mouse pubmed reference national center for biotechnology information u s national library of medicine collins t williams a johnston gi kim j eddy r shows t et al february 1991 structure and chromosomal location of the gene for endothelial leukocyte adhesion molecule 1 the journal of biological chemistry 266 4 2466 73 doi 10 1016 s0021 9258 18 52267 5 pmid 1703529 graves bj crowther rl chandran c rumberger jm li s huang ks et al february 1994 insight into e selectin ligand interaction from the crystal structure and mutagenesis of the lec egf domains nature 367 6463 532 8 bibcode 1994natur 367 532g doi 10 1038 367532a0 pmid 7509040 s2cid 4338500 somers ws tang j shaw gd camphausen rt october 2000 insights into the molecular basis of leukocyte tethering and rolling revealed by structures of p and e selectin bound to sle x and psgl 1 cell 103 3 467 79 doi 10 1016 s0092 8674 00 00138 0 pmid 11081633 s2cid 12719907 cummings rd 2008 selectins in varki a cummings rd esko jd freeze hh stanley p bertozzi cr hart gw etzler me eds essentials of glycobiology 2nd ed plai...
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