The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD ) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophenotyping of cells. In terms of physiology, CD molecules can act in numerous ways, often acting as receptors or ligands important to the cell. A signal cascade is usually initiated, altering the behavior of the cell (see cell signaling ). Some CD proteins do not play a role in cell signaling, but have other functions, such as cell adhesion . CD for humans is numbered up to 371 (as of 21 April 2016 ).
59-717: 4H2B , 4H1Y , 4H2F , 4H2I , 4H1S , 4H2G 4907 23959 ENSG00000135318 ENSMUSG00000032420 P21589 Q61503 NM_002526 NM_001204813 NM_011851 NP_001191742 NP_002517 NP_035981 5′-nucleotidase (5′-NT), also known as ecto-5′-nucleotidase or CD73 ( cluster of differentiation 73), is an enzyme that in humans is encoded by the NT5E gene . CD73 commonly serves to convert AMP to adenosine . NT5E contains binding sites for transcription factors AP-2, SMAD proteins, SP-1 and elements responsive to c-AMP , which can be found in c-AMP promoter parts. SMADs 2, 3, 4 and 5 and SP-1 are binding to
118-410: A chemokine receptor on the surface of a T helper cell to gain entry. The number of CD4 and CD8 T cells in blood is often used to monitor the progression of HIV infection . While CD molecules are very useful in defining leukocytes, they are not merely markers on the cell surface . Though only a fraction of known CD molecules have been thoroughly characterised, most of them have important functions. In
177-575: A stem cell , as opposed to a fully differentiated endothelial cell . Some cell populations can also be defined as , , or (alternatively, , , or ), indicating an overall variability in CD expression , particularly when compared to other cells being studied. A review of the development of T cells in the thymus uses this nomenclature to identify cells transitioning from CD4 /CD8 double-positive cells to CD4 /CD8 . Since 1982 there have been nine Human Leukocyte Differentiation Antigen Workshops culminating in
236-529: A broad range of proteins. Neutrophils have three methods for directly attacking microorganisms: phagocytosis (ingestion), degranulation (release of soluble anti-microbials), and generation of neutrophil extracellular traps (NETs). Neutrophils are phagocytes , capable of ingesting microorganisms or particles. For targets to be recognized, they must be coated in opsonins – a process known as antibody opsonization . They can internalize and kill many microbes , each phagocytic event resulting in
295-481: A characteristic lobed appearance, the separate lobes connected by chromatin . The nucleolus disappears as the neutrophil matures, which is something that happens in only a few other types of nucleated cells. Up to 17% of female human neutrophil nuclei have a drumstick-shaped appendage which contains the inactivated X chromosome . In the cytoplasm, the Golgi apparatus is small, mitochondria and ribosomes are sparse, and
354-426: A conference. The CD system is commonly used as cell markers in immunophenotyping , allowing cells to be defined based on what molecules are present on their surface. These markers are often used to associate cells with certain immune functions . While using one CD molecule to define populations is uncommon (though a few examples exist), combining markers has allowed for cell types with very specific definitions within
413-600: A dimer of 2 identical 70-kD subunits bound by a glycosyl phosphatidyl inositol linkage to the external face of the plasma membrane. The enzyme is used as a marker of lymphocyte differentiation. Consequently, a deficiency of NT5 occurs in a variety of immunodeficiency diseases (e.g., see MIM 102700, MIM 300300). Other forms of 5-prime nucleotidase exist in the cytoplasm and lysosomes and can be distinguished from ecto-NT5 by their substrate affinities, requirement for divalent magnesium ion, activation by ATP, and inhibition by inorganic phosphate. Rare allelic variants are associated with
472-408: A focus of infection , attracted by cytokines expressed by activated endothelium , mast cells , and macrophages . Neutrophils express and release cytokines, which in turn amplify inflammatory reactions by several other cell types. In addition to recruiting and activating other cells of the immune system, neutrophils play a key role in the front-line defense against invading pathogens, and contain
531-486: A mutation in the pyrin (or marenostrin ) gene, which is expressed mainly in neutrophil granulocytes, leads to a constitutively active acute-phase response and causes attacks of fever , arthralgia , peritonitis , and – eventually – amyloidosis . Hyperglycemia can lead to neutrophil dysfunction. Dysfunction in the neutrophil biochemical pathway myeloperoxidase as well as reduced degranulation are associated with hyperglycemia. The Absolute neutrophil count (ANC)
590-404: A nucleus divided into 2–5 lobes. Neutrophils are a type of phagocyte and are normally found in the bloodstream . During the beginning ( acute ) phase of inflammation , particularly as a result of bacterial infection , environmental exposure, and some cancers, neutrophils are one of the first responders of inflammatory cells to migrate toward the site of inflammation. They migrate through
649-685: A particularly important role for NETs in sepsis , where NETs are formed within blood vessels. Finally, NET formation has been demonstrated to augment macrophage bactericidal activity during infection. Recently, NETs have been shown to play a role in inflammatory diseases, as NETs could be detected in preeclampsia , a pregnancy-related inflammatory disorder in which neutrophils are known to be activated. Neutrophil NET formation may also impact cardiovascular disease , as NETs may influence thrombus formation in coronary arteries . NETs are now known to exhibit pro- thrombotic effects both in vitro and in vivo . More recently, in 2020 NETs were implicated in
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#1732883949208708-462: A process called degranulation . The contents of these granules have antimicrobial properties, and help combat infection. Glitter cells are polymorphonuclear leukocyte neutrophils with granules. In 2004, Brinkmann and colleagues described a striking observation that activation of neutrophils causes the release of web-like structures of DNA; this represents a third mechanism for killing bacteria. These neutrophil extracellular traps (NETs) comprise
767-403: A reactive oxygen species. Superoxide decays spontaneously or is broken down via enzymes known as superoxide dismutases (Cu/ZnSOD and MnSOD), to hydrogen peroxide, which is then converted to hypochlorous acid (HClO), by the green heme enzyme myeloperoxidase . It is thought that the bactericidal properties of HClO are enough to kill bacteria phagocytosed by the neutrophil, but this may instead be
826-648: A step necessary for the activation of proteases. Though neutrophils can kill many microbes, the interaction of neutrophils with microbes and molecules produced by microbes often alters neutrophil turnover. The ability of microbes to alter the fate of neutrophils is highly varied, can be microbe-specific, and ranges from prolonging the neutrophil lifespan to causing rapid neutrophil lysis after phagocytosis. Chlamydia pneumoniae and Neisseria gonorrhoeae have been reported to delay neutrophil apoptosis . Thus, some bacteria – and those that are predominantly intracellular pathogens – can extend
885-434: A surface, neutrophil granulocytes have an average diameter of 12–15 micrometers (μm) in peripheral blood smears . In suspension, human neutrophils have an average diameter of 8.85 μm. With the eosinophil and the basophil , they form the class of polymorphonuclear cells , named for the nucleus ' multilobulated shape (as compared to lymphocytes and monocytes , the other types of white cells). The nucleus has
944-483: A syndrome of adult-onset calcification of joints and arteries (CALJA) affecting the iliac , femoral , and tibial arteries reducing circulation in the legs and the joints of the hands and feet causing pain. NT5E (CD73) is a surface enzyme which is expressed on multiple cells. This enzyme mediates the gradual hydrolysis of the autocrine and paracrine danger signals of ATP and ADP to anti-inflammatory adenosine . Immune suppression mediated by adenosinergic pathways
1003-744: A type of phagocytic white blood cell and part of innate immunity . More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in different animals. They are also known as neutrocytes, heterophils or polymorphonuclear leukocytes. They are formed from stem cells in the bone marrow and differentiated into subpopulations of neutrophil-killers and neutrophil-cagers. They are short-lived (between 5 and 135 hours, see § Life span ) and highly mobile, as they can enter parts of tissue where other cells/molecules cannot. Neutrophils may be subdivided into segmented neutrophils and banded neutrophils (or bands ). They form part of
1062-429: A web of fibers composed of chromatin and serine proteases that trap and kill extracellular microbes. It is suggested that NETs provide a high local concentration of antimicrobial components and bind, disarm, and kill microbes independent of phagocytic uptake. In addition to their possible antimicrobial properties, NETs may serve as a physical barrier that prevents further spread of pathogens. Trapping of bacteria may be
1121-433: Is 28:1:25. Neutrophils are much more numerous than the longer-lived monocyte / macrophage phagocytes. A pathogen (disease-causing microorganism or virus) is likely to first encounter a neutrophil. Some experts hypothesize that the short lifetime of neutrophils is an evolutionary adaptation. The short lifetime of neutrophils minimizes propagation of those pathogens that parasitize phagocytes (e.g. Leishmania ) because
1180-462: Is a standard normal range. People of African and Middle Eastern descent may have lower counts, which are still normal. A report may divide neutrophils into segmented neutrophils and bands . When circulating in the bloodstream and inactivated, neutrophils are spherical. Once activated, they change shape and become more amorphous or amoeba -like and can extend pseudopods as they hunt for antigens . The capacity of neutrophils to engulf bacteria
1239-427: Is also used in diagnosis and prognosis. ANC is the gold standard for determining severity of neutropenia, and thus neutropenic fever. Any ANC < 1500 cells / mm is considered neutropenia, but <500 cells / mm is considered severe. There is also new research tying ANC to myocardial infarction as an aid in early diagnosis. Neutrophils promote ventricular tachycardia in acute myocardial infarction. In autopsy ,
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#17328839492081298-453: Is an important key molecule in cancer regulation and development and is involved in tumor progression. In addition, NT5E functions as an adhesion and signaling molecule and can regulate cellular signaling with extracellular matrix components such as fibronectin and laminin . This can mediate the metastatic and invasive properties of cancer. In mouse breast and prostate cancer tumor models as well as in breast cancer xenograft model , NT5E
1357-469: Is located on the αL integrin unit ( CD11a ). Two functionally unequal subpopulations of neutrophils were identified on the basis of different levels of their reactive oxygen metabolite generation, membrane permeability, activity of enzyme system, and ability to be inactivated. The cells of one subpopulation with high membrane permeability (neutrophil-killers) intensively generate reactive oxygen metabolites and are inactivated in consequence of interaction with
1416-479: Is missing, which shows an impaired regulatory function of T cells. NT5E can act as an immune inhibitory control molecule. Free adenosine generated by NT5E inhibits cellular immune responses and thereby promotes immune escape of tumor cells. Due to enzymatic and non-enzymatic properties, CD73 is involved in cancer-related processes and is upregulated in many cancers such as leukemia , glioblastoma , melanoma , oesophageal , prostate , ovarian and breast cancer . It
1475-411: Is reduced when simple sugars like glucose, fructose as well as sucrose, honey and orange juice were ingested, while the ingestion of starches had no effect. Fasting, on the other hand, strengthened the neutrophils' phagocytic capacity to engulf bacteria. It was concluded that the function, and not the number, of phagocytes in engulfing bacteria was altered by the ingestion of sugars. In 2007 researchers at
1534-445: Is very important for maintaining immune system homeostasis. Immune suppressive functions of T regulatory cells are also dependent on CD73 expression. Treg's generally suppress the immune response. They affect proliferation and function of T cell. CD73 also occurs on anergic CD4 + T cells, thereby maintaining self tolerance to healthy tissues as well as protecting the fetus from the mother's immune system during pregnancy. Also described
1593-522: The phosphoinositide 3-kinases ( PI3Ks ). In neutrophils, lipid products of PI3Ks regulate activation of Rac1, hematopoietic Rac2, and RhoG GTPases of the Rho family and are required for cell motility . Ras-GTPases and Rac-GTPases regulate cytoskeletal dynamics and facilitate neutrophils adhesion, migration, and spreading. They accumulate asymmetrically to the plasma membrane at the leading edge of polarized cells. Spatially regulating Rho GTPases and organizing
1652-414: The polymorphonuclear cells family (PMNs) together with basophils and eosinophils . The name neutrophil derives from staining characteristics on hematoxylin and eosin ( H&E ) histological or cytological preparations. Whereas basophilic white blood cells stain dark blue and eosinophilic white blood cells stain bright red, neutrophils stain a neutral pink. Normally, neutrophils contain
1711-488: The NT5E promoter in rats, as was proven in chromatin immunoprecipitation assays. Due to the fact, that the human and rat NT5E transcripts are 89% identical, human NT5E could be also regulated by SMAD proteins. Ecto-5-prime-nucleotidase (5-prime-ribonucleotide phosphohydrolase; EC 3.1.3.5) catalyzes the conversion at neutral pH of purine 5-prime mononucleotides to nucleosides, the preferred substrate being AMP . The enzyme consists of
1770-565: The Whitehead Institute of Biomedical Research found that given a selection of sugars on microbial surfaces, the neutrophils reacted to some types of sugars preferentially. The neutrophils preferentially engulfed and killed beta-1,6-glucan targets compared to beta-1,3-glucan targets. The average lifespan of inactivated human neutrophils in the circulation has been reported by different approaches to be between 5 and 135 hours. Upon activation, they marginate (position themselves adjacent to
1829-399: The blood smear and is positive when most or all of the neutrophils have 5 or more segments. Neutrophils are the most abundant white blood cells in the human body (approximately 10 are produced daily); they account for approximately 50–70% of all white blood cells (leukocytes). The stated normal range for human blood counts varies between laboratories, but a neutrophil count of 2.5–7.5 × 10 /L
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1888-415: The blood vessel endothelium) and undergo selectin -dependent capture followed by integrin -dependent adhesion in most cases, after which they migrate into tissues, where they survive for 1–2 days. Neutrophils have also been demonstrated to be released into the blood from a splenic reserve following myocardial infarction . The distribution ratio of neutrophils in bone marrow, blood and connective tissue
1947-403: The blood vessels and then through interstitial space, following chemical signals such as interleukin-8 (IL-8), C5a , fMLP , leukotriene B4 , and hydrogen peroxide (H 2 O 2 ) in a process called chemotaxis . They are the predominant cells in pus , accounting for its whitish/yellowish appearance. Neutrophils are recruited to the site of injury within minutes following trauma and are
2006-422: The cancer treatment. MicroRNA are small non-coding RNA molecules which regulate gene expression at posttranscriptional level via binding to mRNA. This leads to degradation of the target mRNA molecule or translational repression . In tumor cells the miRNA expression pattern often change and therefore affect the surface NT5E, which as result interfere the anti-tumor immune response. For example, studies confirm
2065-404: The cell surface are involved in this process. Neutrophils undergo a process called chemotaxis via amoeboid movement , which allows them to migrate toward sites of infection or inflammation. Cell surface receptors allow neutrophils to detect chemical gradients of molecules such as interleukin-8 (IL-8), interferon gamma (IFN-γ), C3a, C5a , and leukotriene B4 , which these cells use to direct
2124-426: The designation (e.g., CD2 molecule). Currently, "CD2" is generally used to designate the molecule, and "CD2 antibody " is used to designate the antibody. Cell populations are usually defined using a '+' or a '−' symbol to indicate whether a certain cell fraction expresses or lacks a CD molecule. For example, a " CD34 +, CD31 −" cell is one that expresses CD34 but not CD31. This CD combination typically corresponds to
2183-411: The enzyme in extracellular space. Unregulated activity of neutrophil elastase can lead to disruption of pulmonary barrier showing symptoms corresponding with acute lung injury . The enzyme also influences activity of macrophages by cleaving their toll-like receptors (TLRs) and downregulating cytokine expression by inhibiting nuclear translocation of NF-κB . In Familial Mediterranean fever (FMF),
2242-423: The example of CD4 and CD8, these molecules are critical in antigen recognition. Others (e.g., CD135 ) act as cell surface receptors for growth factors . Recently, the marker CD47 was found to have anti- phagocytic signals to macrophages and inhibit natural killer (NK) cells. This enabled researchers to apply CD47 as a potential target to attenuate immune rejection . Neutrophils Neutrophils are
2301-408: The formation of a phagosome into which reactive oxygen species and hydrolytic enzymes are secreted. The consumption of oxygen during the generation of reactive oxygen species has been termed the " respiratory burst ", although unrelated to respiration or energy production. The respiratory burst involves the activation of the enzyme NADPH oxidase , which produces large quantities of superoxide ,
2360-466: The formation of blood clots in cases of severe COVID-19 . TANs can exhibit an elevated extracellular acidification rate when there is an increase in glycolysis levels. When there is a metabolic shift in TANs this can lead to tumor progression in certain areas of the body, such as the lungs. TANs support the growth and progression of tumors unlike normal neutrophils which would inhibit tumor progression through
2419-423: The function of these immune cells. In addition, the tumor cells may also express adenosine A1 and A3 receptors associated with Gαi proteins, promoting both the migration and proliferation of tumor cells. Especially due to its beneficial effects in mouse tumor model , anti-CD73 therapy is now a promising approach to cancer treatment in the future. CD73 inhibitor are currently being tested in clinical trials for
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2478-446: The hallmark of acute inflammation. They not only play a central role in combating infection but also contribute to pain in the acute period by releasing pro-inflammatory cytokines and other mediators that sensitize nociceptors, leading to heightened pain perception. However, due to some pathogens being indigestible, they may not be able to resolve certain infections without the assistance of other types of immune cells. When adhered to
2537-509: The immune system. CD molecules are utilized in cell sorting using various methods, including flow cytometry . Two commonly used CD molecules are CD4 and CD8 , which are, in general, used as markers for helper and cytotoxic T cells, respectively. These molecules are defined in combination with CD3+, as some other leukocytes also express these CD molecules (some macrophages express low levels of CD4; dendritic cells express high levels of CD8). Human immunodeficiency virus binds CD4 and
2596-495: The leading edge of the cell, PI3Ks and their lipid products could play pivotal roles in establishing leukocyte polarity, as compass molecules that tell the cell where to crawl. It has been shown in mice that in certain conditions neutrophils have a specific type of migration behaviour referred to as neutrophil swarming during which they migrate in a highly coordinated manner and accumulate and cluster to sites of inflammation. Being highly motile , neutrophils quickly congregate at
2655-448: The low affinity Fc-γ receptor IIIb (FCGR3B : CD16b ) The single known HNA-2a antigen is located on CD177 . The HNA-3 antigen system has two antigens (3a and 3b) which are located on the seventh exon of the CLT2 gene ( SLC44A2 ). The HNA-4 and HNA-5 antigen systems each have two known antigens (a and b) and are located in the β2 integrin . HNA-4 is located on the αM chain ( CD11b ) and HNA-5
2714-409: The molecule. If the molecule has not been well characterized or has only one mAb, it is usually given the provisional indicator "w" (as in " CDw186 "). For instance, CD2 mAbs are reagents that react with a 50‐kDa transmembrane glycoprotein expressed on T cells . The CD designations were used to describe the recognized molecules but had to be clarified by attaching the term antigen or molecule to
2773-405: The more time such parasites spend outside a host cell , the more likely they will be destroyed by some component of the body's defenses. Also, because neutrophil antimicrobial products can also damage host tissues , their short life limits damage to the host during inflammation . Neutrophils will be removed after phagocytosis of pathogens by macrophages. PECAM-1 and phosphatidylserine on
2832-452: The neutrophil lifespan by disrupting the normal process of spontaneous apoptosis and/or PICD (phagocytosis-induced cell death). On the other end of the spectrum, some pathogens such as Streptococcus pyogenes are capable of altering neutrophil fate after phagocytosis by promoting rapid cell lysis and/or accelerating apoptosis to the point of secondary necrosis. Neutrophils also release an assortment of proteins in three types of granules by
2891-486: The osteoblasts can promote bone growth thus forming a favorable environment for tumor cells to grow to form bone metastasis. Low neutrophil counts are termed neutropenia . This can be congenital (developed at or before birth) or it can develop later, as in the case of aplastic anemia or some kinds of leukemia . It can also be a side-effect of medication , most prominently chemotherapy . Neutropenia makes an individual highly susceptible to infections. It can also be
2950-479: The path of their migration. Neutrophils have a variety of specific receptors, including ones for complement , cytokines like interleukins and IFN-γ, chemokines , lectins , and other proteins. They also express receptors to detect and adhere to endothelium and Fc receptors for opsonin . In leukocytes responding to a chemoattractant , the cellular polarity is regulated by activities of small Ras or Rho guanosine triphosphatases (Ras or Rho GTPases ) and
3009-441: The phagocytosis of tumor cells. Utilizing a mouse model, they identified that both Glut1 and glucose metabolism increased in TANs found within a mouse who possessed lung adenocarcinoma. A study showed that lung tumor cells can remotely initiate osteoblasts and these osteoblasts can worsen tumors in two ways. First, they can induce SiglecF -expressing neutrophil formation that in turn promotes lung tumor growth and progression. Second,
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#17328839492083068-698: The presence of neutrophils in the heart or brain is one of the first signs of infarction, and is useful in the timing and diagnosis of myocardial infarction and stroke . Just like phagocytes, pathogens may evade or infect neutrophils. Some bacterial pathogens evolved various mechanisms such as virulence molecules to avoid being killed by neutrophils. These molecules collectively may alter or disrupt neutrophil recruitment, apoptosis or bactericidal activity. Neutrophils can also serve as host cell for various parasites that infects them avoding phagocytosis, including: There are five (HNA 1–5) sets of neutrophil antigens recognized. The three HNA-1 antigens (a-c) are located on
3127-460: The result of colonization by intracellular neutrophilic parasites. In alpha 1-antitrypsin deficiency , the important neutrophil elastase is not adequately inhibited by alpha 1-antitrypsin , leading to excessive tissue damage in the presence of inflammation – the most prominent one being emphysema . Negative effects of elastase have also been shown in cases when the neutrophils are excessively activated (in otherwise healthy individuals) and release
3186-587: The role of the miR30 family in NT5E regulation. Upon miR-30a-5p expression, NT5E expression was decreased. This article incorporates text from the United States National Library of Medicine , which is in the public domain . Cluster of differentiation The CD nomenclature was proposed and established in the 1st International Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA), held in Paris in 1982. This system
3245-414: The rough endoplasmic reticulum is absent. The cytoplasm also contains about 200 granules, of which a third are azurophilic . Neutrophils will show increasing segmentation (many segments of the nucleus) as they mature. A normal neutrophil should have 3–5 segments. Hypersegmentation is not normal but occurs in some disorders, most notably vitamin B 12 deficiency . This is noted in a manual review of
3304-402: The substrate, whereas cells of another subpopulation (neutrophil-cagers) produce reactive oxygen species less intensively, don't adhere to substrate and preserve their activity. Additional studies have shown that lung tumors can be infiltrated by various populations of neutrophils. Neutrophils display highly directional amoeboid motility in infected footpad and phalanges. Intravital imaging
3363-626: Was adenosine generated by NT5E, which limits the inflammatory immune response by negative feedback in neutrophil which express the adenosine receptor . Some tumours have upregulation and overexpression of CD73 so it has been proposed as a drug target for cancer therapy. An anti-CD73 antibody CPI-006 has started early stage clinical trials as a treatment for advanced cancers. Specialized immune cells such as myeloid-derived suppressor cells and regulatory T cells also mediate their effects via adenosine generated by local ectonucleotidase. In some cases of lupus patients, adequate T cell expression of CD73
3422-550: Was confirmed to support tumor angiogenesis . His expression promotes invasion and metastasis of murine and human melanoma cells and human breast cancer cells. Tumor infiltration by cells which express NT5E such as myeloid derived suppressor cells (MDSC), Treg's, dendritic cells (DC) leads to accumulation of adenosine. Subsequently, cAMP signaling is triggered in T cell that express the adenosine A2A receptor . Adenosine receptor are also expressed on macrophage , DCs, MDSC and natural killer cell (NK). Thus, adenosine may inhibit
3481-461: Was intended for the classification of the many monoclonal antibodies (mAbs) generated by different laboratories around the world against epitopes on the surface molecules of leukocytes (white blood cells). Since then, its use has expanded to many other cell types, and more than 370 CD unique clusters and subclusters have been identified. The proposed surface molecule is assigned a CD number once two specific monoclonal antibodies are shown to bind to
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