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68-567: 1ESL , 1G1T , 4C16 , 4CSY 6401 20339 ENSG00000007908 ENSMUSG00000026582 P16581 Q00690 NM_000450 NM_011345 NP_000441 NP_035475 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

136-446: A blue hue. The nucleus is bi- or tri-lobed, but it is hard to see because of the number of coarse granules that hide it. They secrete two chemicals that aid in the body's defenses: histamine and heparin . Histamine is responsible for widening blood vessels and increasing the flow of blood to injured tissue. It also makes blood vessels more permeable so neutrophils and clotting proteins can get into connective tissue more easily. Heparin

204-647: 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. 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. while experimental lung metastasis

272-571: A patient’s bone marrow . Researchers have developed a way to use selectins to direct stem cells introduced into the vascular system to the bone marrow. E-selectins are constitutively expressed in the bone marrow, and researchers have shown that tagging stem cells with a certain glycoprotein causes these cells to migrate to the bone marrow. Thus, selectins may someday be essential to a regenerative therapy for osteoporosis. Leukocyte White blood cells (scientific name leukocytes ), also called immune cells or immunocytes , are cells of

340-595: 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. In cancer cells, CD44 , death receptor-3 (DR3), LAMP1 , and LAMP2 were identified as E-selectin ligands present on colon cancer cells, and CD44v , Mac2-BP , and gangliosides were identified as E-selectin ligands present on breast cancer cells. On human neutrophils

408-415: A role in inflammation and progression of cancer. Tumor cells exploit the selectin-dependent mechanisms mediating cell tethering and rolling interactions through recognition of carbohydrate ligands on tumor cell to enhance distant organ metastasis, showing ‘leukocyte mimicry’. A number of studies have shown increased expression of carbohydrate ligands on metastatic tumor, enhanced E-selectin expression on

476-986: 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. 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. In addition, E-selectin may also function to recruit monocytes to primary tumors or lung metastases to promote an inflammatory pro-tumor microenvironment. Blocking these interactions or enabling trafficking of CAR-T cells to E-selectin-positive sites may hold promise for future therapeutic development. In cases of elevated blood glucose levels, such as in sepsis, E-selectin expression

544-583: A specific organ. The differential selectin expression profile on endothelium and the specific interactions of selectins expressed by endothelial cells of potential target organs and their ligands expressed on cancer cells are major determinants that underlie the organ-specific distribution of metastases. Selectins are involved in projects to treat osteoporosis, a disease that occurs when bone-creating cells called osteoblasts become too scarce. Osteoblasts develop from stem cells , and scientists hope to eventually be able to treat osteoporosis by adding stem cells to

612-528: A thin strand. The cytoplasm is full of granules that assume a characteristic pink-orange color with eosin staining. Basophils are chiefly responsible for allergic and antigen response by releasing the chemical histamine causing the dilation of blood vessels . Because they are the rarest of the white blood cells (less than 0.5% of the total count) and share physicochemical properties with other blood cells, they are difficult to study. They can be recognized by several coarse, dark violet granules, giving them

680-550: A variable number of consensus repeat units (2, 6, and 9 for L-, E-, and P-selectin, respectively), a transmembrane domain (TM) and an intracellular cytoplasmic tail (cyto). The transmembrane and cytoplasmic parts are not conserved across the selectins being responsible for their targeting to different compartments. Though they share common elements, their tissue distribution and binding kinetics are quite different, reflecting their divergent roles in various pathophysiological processes. There are three subsets of selectins: L-selectin

748-586: A weakened immune system. The name "white blood cell" derives from the physical appearance of a blood sample after centrifugation . White cells are found in the buffy coat , a thin, typically white layer of nucleated cells between the sedimented red blood cells and the blood plasma . The scientific term leukocyte directly reflects its description. It is derived from the Greek roots leuk - meaning "white" and cyt - meaning "cell". The buffy coat may sometimes be green if there are large amounts of neutrophils in

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816-522: Is qualitatively . There are various disorders in which the number of white blood cells is normal but the cells do not function normally. Neoplasia of white blood cells can be benign but is often malignant . Of the various tumors of the blood and lymph , cancers of white blood cells can be broadly classified as leukemias and lymphomas , although those categories overlap and are often grouped together. A range of disorders can cause decreases in white blood cells. This type of white blood cell decreased

884-430: Is also a high-efficiency ligand for endothelium-expressed E-selectin under flow. 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. 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

952-470: Is an anticoagulant that inhibits blood clotting and promotes the movement of white blood cells into an area. Basophils can also release chemical signals that attract eosinophils and neutrophils to an infection site. Lymphocytes are much more common in the lymphatic system than in blood. Lymphocytes are distinguished by having a deeply staining nucleus that may be eccentric in location, and a relatively small amount of cytoplasm. Lymphocytes include: Monocytes,

1020-466: Is an important subset of the complete blood count . The normal white cell count is usually between 4 × 10 /L and 1.1 × 10 /L. In the US, this is usually expressed as 4,000 to 11,000 white blood cells per microliter of blood. White blood cells make up approximately 1% of the total blood volume in a healthy adult, making them substantially less numerous than the red blood cells at 40% to 45% . However, this 1% of

1088-414: Is associated with ACS, and it might be a risk factor for ACS. 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

1156-638: Is by lineage: Myeloid cells (neutrophils, monocytes, eosinophils and basophils) are distinguished from lymphoid cells (lymphocytes) by hematopoietic lineage ( cellular differentiation lineage). Lymphocytes can be further classified as T cells, B cells, and natural killer cells. Neutrophils are the most abundant white blood cell, constituting 60–70% of the circulating leukocytes. They defend against bacterial or fungal infection. They are usually first responders to microbial infection; their activity and death in large numbers form pus . They are commonly referred to as polymorphonuclear (PMN) leukocytes, although, in

1224-493: 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. It's also found that E-selectin expression increased in human ruptured cerebral aneurysm tissues. E-selectin might be an important factor involved in

1292-497: Is encoded by the SELE gene . 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. The structure reveals limited contact between

1360-401: Is expressed on endothelial cells first, followed by E-selectin later. Stimuli such as histamine and thrombin cause endothelial cells to mobilize immediate release of preformed P-selectin from Weible-Palade bodies inside the cell. Cytokines such as TNF-alpha stimulate transcription and translation of E-selectin and additional P-selectin, which account for the delay of several hours. As

1428-491: 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). Traditional Chinese herbal medicines, like berberine downregulate E-selectin. Study shows

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1496-426: Is less frequently used now. Produced in the bone marrow , white blood cells defend the body against infections and disease . An excess of white blood cells is usually due to infection or inflammation. Less commonly, a high white blood cell count could indicate certain blood cancers or bone marrow disorders. The number of leukocytes in the blood is often an indicator of disease , and thus the white blood cell count

1564-427: Is most commonly caused by inflammation . There are four major causes: increase of production in bone marrow, increased release from storage in bone marrow, decreased attachment to veins and arteries, decreased uptake by tissues. Leukocytosis may affect one or more cell lines and can be neutrophilic, eosinophilic, basophilic, monocytosis, or lymphocytosis. Neutrophilia is an increase in the absolute neutrophil count in

1632-685: Is not affected by the genetic deletion of E-selectin. Furthermore, studies have also shown that primary tumor growth is increased in E-selectin knockout mice. This paradox was more recently solved by a trio of studies showing that E-selectin is only constitutively expressed in the bone marrow endothelium where it is thought to perform functions vital to hematopoiesis . that are hijacked specifically by cells metastasizing to bone and not other sites. This data supports ongoing clinical efforts to inhibit breast cancer bone metastasis with E-selectin-blocking agents. The complexity of E-selectin ligand biology may also play

1700-472: Is not complete. Symptoms of neutropenia are associated with the underlying cause of the decrease in neutrophils. For example, the most common cause of acquired neutropenia is drug-induced, so an individual may have symptoms of medication overdose or toxicity. Treatment is also aimed at the underlying cause of the neutropenia. One severe consequence of neutropenia is that it can increase the risk of infection. Defined as total lymphocyte count below 1.0x10 /L,

1768-479: Is rapidly induced by inflammatory cytokines. These three types share a significant degree of sequence homology among themselves (except in the transmembrane and cytoplasmic domains) and between species. Analysis of this homology has revealed that the lectin domain, which binds sugars, is most conserved, suggesting that the three selectins bind similar sugar structures. The cytoplasmic and transmembrane domains are highly conserved between species, but not conserved across

1836-412: Is sometimes not expressed constitutively and the cancer cells have to trigger their expression. In this context, the culture supernatants of cancer cells can trigger the expression of E- selectin by endothelial cells suggesting that cancer cells may release by themselves cytokines such as TNF-α, IL-1β or INF-γ that will directly activate endothelial cells to express E-selectin, P-selectin, ICAM-2 or VCAM. On

1904-576: Is stimulated by tumor necrosis factor α ( TNFα ), interleukin-1 ( IL-1 ) and lipopolysaccharide ( LPS ). 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. 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

1972-497: Is the smallest of the vascular selectins, expressed on all granulocytes and monocytes and on most lymphocytes, can be found in most leukocytes. P-selectin, the largest selectin, is stored in α-granules of platelets and in Weibel–Palade bodies of endothelial cells, and is translocated to the cell surface of activated endothelial cells and platelets. E-selectin is not expressed under baseline conditions, except in skin microvessels, but

2040-418: Is usually the neutrophil. In this case the decrease may be called neutropenia or granulocytopenia. Less commonly, a decrease in lymphocytes (called lymphocytopenia or lymphopenia) may be seen. Neutropenia can be acquired or intrinsic . A decrease in levels of neutrophils on lab tests is due to either decreased production of neutrophils or increased removal from the blood. The following list of causes

2108-569: The Lewis X and Lewis A families found on monocytes , granulocytes , and T-lymphocytes . 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

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2176-424: The immune system that are involved in protecting the body against both infectious disease and foreign invaders. White blood cells are generally larger than red blood cells. They include three main subtypes: granulocytes , lymphocytes and monocytes . All white blood cells are produced and derived from multipotent cells in the bone marrow known as hematopoietic stem cells . Leukocytes are found throughout

2244-601: The leukocyte adhesion cascade . Each selectin has a carbohydrate recognition domain that mediates binding to specific glycans on apposing cells. They have remarkably similar protein folds and carbohydrate binding residues, leading to overlap in the glycans to which they bind. Selectins bind to the sialyl Lewis X (SLe ) determinant “NeuAcα2-3Galβ1-4(Fucα1-3)GlcNAc.” However, SLe , per se, does not constitute an effective selectin receptor. Instead, SLe and related sialylated, fucosylated glycans are components of more extensive binding determinants. The best-characterized ligand for

2312-464: The peripheral circulation . Normal blood values vary by age. Neutrophilia can be caused by a direct problem with blood cells (primary disease). It can also occur as a consequence of an underlying disease (secondary). Most cases of neutrophilia are secondary to inflammation. Primary causes Secondary causes A normal eosinophil count is considered to be less than 0.65 × 10 /L. Eosinophil counts are higher in newborns and vary with age, time (lower in

2380-469: The E-selectin cytosolic domain derives from two exons. The E-selectin locus flanks the L-selectin locus on chromosome 1. 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,

2448-521: 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 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

2516-436: 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

2584-404: The blood makes a large difference to health, because immunity depends on it. An increase in the number of leukocytes over the upper limits is called leukocytosis . It is normal when it is part of healthy immune responses, which happen frequently. It is occasionally abnormal, when it is neoplastic or autoimmune in origin. A decrease below the lower limit is called leukopenia . This indicates

2652-1205: The body, including the blood and lymphatic system . All white blood cells have nuclei , which distinguishes them from the other blood cells , the anucleated red blood cells (RBCs) and platelets . The different white blood cells are usually classified by cell lineage ( myeloid cells or lymphoid cells ). White blood cells are part of the body's immune system. They help the body fight infection and other diseases. Types of white blood cells are granulocytes (neutrophils, eosinophils, and basophils), and agranulocytes ( monocytes , and lymphocytes (T cells and B cells)). Myeloid cells ( myelocytes ) include neutrophils , eosinophils , mast cells , basophils , and monocytes . Monocytes are further subdivided into dendritic cells and macrophages . Monocytes, macrophages, and neutrophils are phagocytic . Lymphoid cells ( lymphocytes ) include T cells (subdivided into helper T cells , memory T cells , cytotoxic T cells ), B cells (subdivided into plasma cells and memory B cells ), and natural killer cells . Historically, white blood cells were classified by their physical characteristics ( granulocytes and agranulocytes ), but this classification system

2720-440: The cancer cells. Metastatic cells that show a high propensity to metastasize to certain organs adhere at higher rates to venular endothelial cells isolated from these target sites. Moreover, they invade the target tissue at higher rates and respond better to paracrine growth factors released from the target site. Typically, the cancer cell/endothelial cell interactions imply first a selectin-mediated initial attachment and rolling of

2788-406: The cells most commonly affected are CD4+ T cells. Like neutropenia, lymphocytopenia may be acquired or intrinsic and there are many causes. This is not a complete list. Like neutropenia, symptoms and treatment of lymphocytopenia are directed at the underlying cause of the change in cell counts. An increase in the number of white blood cells in circulation is called leukocytosis . This increase

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2856-485: The circulating cancer cells on the endothelium. The rolling cancer cells then become activated by locally released chemokines present at the surface of endothelial cells. This triggers the activation of integrins from the cancer cells allowing their firmer adhesion to members of the Ig-CAM family such as ICAM, initiating the transendothelial migration and extravasation processes.[72] The appropriate set of endothelial receptors

2924-768: The day, seasonally, and during menstruation . It rises in response to allergies, parasitic infections, collagen diseases, and disease of the spleen and central nervous system. They are rare in the blood, but numerous in the mucous membranes of the respiratory, digestive, and lower urinary tracts. They primarily deal with parasitic infections. Eosinophils are also the predominant inflammatory cells in allergic reactions. The most important causes of eosinophilia include allergies such as asthma, hay fever, and hives; and parasitic infections. They secrete chemicals that destroy large parasites, such as hookworms and tapeworms, that are too big for any one white blood cell to phagocytize. In general, their nuclei are bi-lobed. The lobes are connected by

2992-429: The endothelial surface and begin making their way into the tissue. 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. 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. This led to

3060-635: The five main types: neutrophils , eosinophils , basophils , lymphocytes , and monocytes . A good way to remember the relative proportions of WBCs is "Never Let Monkeys Eat Bananas". These types are distinguished by their physical and functional characteristics. Monocytes and neutrophils are phagocytic . Further subtypes can be classified. Granulocytes are distinguished from agranulocytes by their nucleus shape (lobed versus round, that is, polymorphonuclear versus mononuclear) and by their cytoplasm granules (present or absent, or more precisely, visible on light microscopy or not thus visible). The other dichotomy

3128-482: 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. 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. Leukocytes in

3196-588: 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 . Studies since have showed that E-selectin binding to colon cancer cells correlates with increasing metastatic potential, and that cancer cells of multiple tumor types bind E-selectin using glycoprotein or glycolipid ligands normally expressed on immune cells. Studies have further described

3264-644: The interaction between host E-selectin and pathogen Pgm6/7 mediates P. gingivalis adherence to endothelial cells and may trigger vascular inflammation. 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

3332-539: The largest type of white blood cell, share the "vacuum cleaner" ( phagocytosis ) function of neutrophils, but are much longer lived as they have an extra role: they present pieces of pathogens to T cells so that the pathogens may be recognized again and killed. This causes an antibody response to be mounted. Monocytes eventually leave the bloodstream and become tissue macrophages , which remove dead cell debris as well as attack microorganisms. Neither dead cell debris nor attacking microorganisms can be dealt with effectively by

3400-406: The leukocyte rolls along the blood vessel wall, the distal lectin-like domain of the selectin binds to certain carbohydrate groups presented on proteins (such as PSGL-1 ) on the leukocyte, which slows the cell and allows it to leave the blood vessel and enter the site of infection. The low-affinity nature of selectins is what allows the characteristic "rolling" action attributed to leukocytes during

3468-655: The liver, which become known as Kupffer cells . These cells still serve a role in the immune system. The two commonly used categories of white blood cell disorders divide them quantitatively into those causing excessive numbers ( proliferative disorders) and those causing insufficient numbers ( leukopenias ). Leukocytosis is usually healthy (e.g., fighting an infection ), but it also may be dysfunctionally proliferative. Proliferative disorders of white blood cells can be classed as myeloproliferative and lymphoproliferative . Some are autoimmune , but many are neoplastic . Another way to categorize disorders of white blood cells

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3536-448: The morning and higher at night), exercise, environment, and exposure to allergens. Eosinophilia is never a normal lab finding. Efforts should always be made to discover the underlying cause, though the cause may not always be found. The complete blood cell count is a blood panel that includes the overall white blood cell count and differential count, a count of each type of white blood cell. Reference ranges for blood tests specify

3604-463: The nanosecond range between ‘open’ and ‘closed’ conformations. Shear stress on the selectin molecule causes it to favor the ‘open’ conformation. In leukocyte rolling, the ‘open’ conformation of the selectin allows it to bind to inward sialyl Lewis molecules farther up along the PSGL-1 chain, increasing overall binding affinity—if the selectin-sialyl Lewis bond breaks, it can slide and form new bonds with

3672-504: The neutrophils. Unlike neutrophils, monocytes are able to replace their lysosomal contents and are thought to have a much longer active life. They have the kidney-shaped nucleus and are typically not granulated. They also possess abundant cytoplasm. Some leucocytes migrate into the tissues of the body to take up a permanent residence at that location rather than remaining in the blood. Often these cells have specific names depending upon which tissue they settle in, such as fixed macrophages in

3740-447: The organ selectivity of metastasis. Several factors may explain the seed and soil theory or homing of metastasis. In particular, genetic regulation and activation of specific chemokines, cytokines and proteases may direct metastasis to a preferred organ. In fact, the extravasation of circulating tumor cells in the host organ requires successive adhesive interactions between endothelial cells and their ligands or counter-receptors present on

3808-487: The other hand, several studies further show that cancer cells may initiate the expression of endothelial adhesion molecules in a more indirect ways. Since the adhesion of several cancer cells to endothelium requires the presence of endothelial selectins as well as sialyl Lewis carbohydrates on cancer cells, the degree of expression of selectins on the vascular wall and the presence of the appropriate ligand on cancer cells are determinant for their adhesion and extravasation into

3876-437: The other sialyl Lewis molecules down the chain. In the ‘closed’ conformation, however, the selectin is only able to bind to one sialyl Lewis molecule, and thus has greatly reduced binding affinity. The result of such is that selectins exhibit catch and slip bond behavior—under low shear stresses, their bonding affinities are actually increased by an increase in tensile force applied to the bond because of more selectins preferring

3944-521: The pathological setting of ischemia/ reperfusion injury while conferring rapid E-selectin down regulation to protect against chronic inflammation. 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. E-selectin recognizes and binds to sialylated carbohydrates present on

4012-524: The process of cerebral aneurysm formation and rupture, by promoting inflammation and weakening cerebral artery walls. E-selectin is also an emerging biomarker for the metastatic potential of some cancers including colorectal cancer and recurrences. Selectin All three known members of the selectin family (L-, E-, and P-selectin) share a similar cassette structure: an N-terminal, calcium-dependent lectin domain, an epidermal growth factor (EGF)-like domain,

4080-498: The pus of wounds. These cells are not able to renew their lysosomes (used in digesting microbes) and die after having phagocytosed a few pathogens. Neutrophils are the most common cell type seen in the early stages of acute inflammation. The average lifespan of inactivated human neutrophils in the circulation has been reported by different approaches to be between 5 and 135 hours. Eosinophils compose about 2–4% of white blood cells in circulating blood. This count fluctuates throughout

4148-467: The sample, due to the heme -containing enzyme myeloperoxidase that they produce. All white blood cells are nucleated, which distinguishes them from the anucleated red blood cells and platelets. Types of leukocytes can be classified in standard ways. Two pairs of broadest categories classify them either by structure ( granulocytes or agranulocytes ) or by cell lineage (myeloid cells or lymphoid cells). These broadest categories can be further divided into

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4216-691: The selectins. These parts of the selectin molecules are responsible for their targeting to different compartments: P-selectin to secretory granules, E-selectin to the plasma membrane, and L-selectin to the tips of microfolds on leukocytes. The name selectin comes from the words "selected" and " lectins ," which are a type of carbohydrate-recognizing protein. Selectins are involved in constitutive lymphocyte homing, and in chronic and acute inflammation processes, including post-ischemic inflammation in muscle, kidney and heart, skin inflammation, atherosclerosis, glomerulonephritis and lupus erythematosus and cancer metastasis. During an inflammatory response , P-selectin

4284-492: The surface of endothelial vessels at the site at tumor metastasis, and the capacity of metastatic tumor cells to roll and adhere to endothelial cells, indicating the role of selectins in metastasis. In addition to E-selectin, the role of P-selectin (expressed on platelets) and L-selectin (on leukocytes) in cancer dissemination has been suggested in the way that they interact with circulating cancer cells at an early stage of metastasis. The selectins and selectin ligands determine

4352-433: 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

4420-445: The technical sense, PMN refers to all granulocytes. They have a multi-lobed nucleus, which consists of three to five lobes connected by slender strands. This gives the neutrophils the appearance of having multiple nuclei, hence the name polymorphonuclear leukocyte. The cytoplasm may look transparent because of fine granules that are pale lilac when stained. Neutrophils are active in phagocytosing bacteria and are present in large amount in

4488-860: The three selectins is P-selectin glycoprotein ligand-1 ( PSGL-1 ), which is a mucin-type glycoprotein expressed on all white blood cells. Neutrophils and eosinophils bind to E-selectin. One of the reported ligands for E-selectin is the sialylated Lewis X antigen (SLe ). Eosinophils, like neutrophils, use sialylated, protease-resistant structures to bind to E-selectin, although the eosinophil expresses much lower levels of these structures on its surface. Ligands for P-selectin on eosinophils and neutrophils are similar sialylated, protease-sensitive, endo-beta-galactosidase-resistant structures, clearly different from those reported for E-selectin, and suggest disparate roles for P-selectin and E-selectin during recruitment during inflammatory responses. Selectins have hinge domains, allowing them to undergo rapid conformational changes in

4556-503: The two domains and a coordination of Ca 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 (SLe; NeuNAcα2,3Galβ1,4[Fucα1,3]GlcNAc) tetrasaccharide was solved in 2000. 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

4624-417: The ‘open’ conformation. At high stresses, the binding affinities are still reduced because the selectin-ligand bond is still a normal slip bond. It is thought that this shear stress threshold helps select for the right diameter of blood vessels to initiate leukocyte extravasation, and may also help prevent inappropriate leukocyte aggregation during vascular stasis. It is becoming evident that selectin may play

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