Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of enzymes as markers of T or B cells in tissue sections has been studied in mouse lymphoid tissue and lymph nodes from the gerbil, rat and cat. Lymphocytes in the T-cell areas of murine lymph nodes and spleen contained discrete dots of non-specific esterase and N-acetyl-beta-D-glucosaminidase (beta-glucosaminidase) activity, with weak acid phosphatase activity. Lymphocytes in the B-cell areas lacked this discrete staining. Cortical thymocytes contained slight esterase activity while medullary thymocytes were strongly positive for both esterase and beta-glucosaminidase. Lymphocytes with a T-cell staining pattern were only occasionally seen in lymph nodes from Nude (nu/nu) mice. ATPase staining was restricted to lymphocytes in the B-cell areas; weak 5'-nucleotidase staining was only present in a frew lymphocytes in both T- and B-cell areas. Blast cells stimulated by in vivo injection of ConA or PHA in the mouse showed strong discrete enzyme activity for non-specific esterase and beta-glucosaminidase. Lipopolysaccharide-stimulated blast cells and cells within germinal centres lacked this discrete staining. Comparison of lymph nodes from the gerbil, rat and cat suggested at least on enzymes as a T-cell marker in each species although considerable variation in staining profiles was seen in the different species.
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PMID:Cytochemical identification of T and B cells in situ in mouse lymphoid tissue and lymph nodes from the rat, gerbil and cat. 8 10

Functional studies were performed on human peripheral blood T lymphocytes stained with goat anti-5'-nucleotidase antibodies and separated into ecto-5'-nucleotidase (ecto-5'-NT)-positive and -negative populations using the FACSTAR fluorescence-activated cell sorter. On the average, ecto-5'-NT+ T cells contained 34 +/- 13% CD4+ and 55 +/- 15% CD8+ cells, whereas ecto-5'-NT-T cells contained 65 +/- 12% CD4+ and 23 +/- 8% CD8+ cells. Staining with anti-5'-NT antibodies did not significantly alter the ability of unseparated T cells to proliferate in response to PHA or PMA, or in a MLR. However, prior incubation with anti-5'-NT antibodies did inhibit the ability of irradiated T cells to provide help for PWM-stimulated Ig synthesis by as much as 55%. In five separate experiments, ecto-5'-NT-T cells demonstrated an equal or better ability to incorporate [3H]TdR after PHA stimulation or in a MLR, as compared with ecto-5'-NT+ T cells. Similarly, ecto-5'-NT- T cells were not diminished in their ability to provide help for autologous B cells in a PWM-driven system. Clearly, the inability of ecto-5'-NT- T cells from patients with a variety of immunodeficiency diseases to function in these assays cannot be explained solely by their lack of ecto-5'-NT activity. In contrast, ecto-5'-NT-positive and -negative T cells showed markedly different dose-response curves for proliferation in response to PMA. Ecto-5'-NT+ T cells responded to lower doses of PMA (1.0 ng/ml) than did ecto-5'-NT- T cells and showed a two- to eight-fold greater rate of [3H]TdR incorporation at 3 to 10 ng of PMA per ml. Ecto-5'-NT+ T cells may have a protein kinase C that is more accessible or more easily activated or may utilize an alternate pathway of activation when stimulated with low concentrations of PMA.
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PMID:Functional characterization of ecto-5'-nucleotidase-positive and -negative human T lymphocytes. 253 56

Human peripheral blood T cells were stimulated to proliferate when cultured with submitogenic doses of PMA and goat antibodies to 5'-nucleotidase (5'-NT). The degree of proliferation, as measured by [3H]TdR incorporation on day 3, was similar to that achieved by stimulation with PHA. Anti-5'-NT antibodies had no effect on PHA-induced proliferation. Maximal stimulation was achieved with 0.6 to 1.0 ng/ml of PMA and 125 micrograms/ml of IgG isolated from a goat anti-5'-NT antiserum. Both intact IgG and F(ab')2 fragments were stimulatory. IL-2R expression and IL-2 secretion were also induced by anti-5'-NT antibodies and PMA. Anti-5'-NT-induced proliferation was inhibited greater than 95% by a murine anti-IL-2 receptor mAb and required less than 0.3% monocytes. Similar results have been obtained with a murine mAb specific for 5'-NT. As expected, anti-5'-NT antibodies and PMA did not induce the proliferation of ecto-5'-NT-T cells isolated by cell sorting. Pretreatment of total T cells with phosphatidylinositol-specific phospholipase C removed an average of 89% of the 5'-NT activity from the cell surface and also inhibited by 83% the ability of the cells to proliferate in response to anti-5'-NT antibodies and PMA. Thus, the activation signal provided by anti-5'-NT antibodies is apparently transduced, in large part, by a form of the enzyme that is attached to the membrane via glycosyl-phosphatidylinositol linkage. These data suggest that 5'-NT may play a role in lymphocyte activation as has been proposed for other glycosyl-phosphatidylinositol-anchored lymphocyte surface proteins.
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PMID:Antibodies to 5'-nucleotidase (CD73), a glycosyl-phosphatidylinositol-anchored protein, cause human peripheral blood T cells to proliferate. 255 May 43

We studied with specific polyclonal and monoclonal antibodies against human ecto-5'-nucleotidase whether the enzyme, located on the surface of human peripheral lymphocytes, could function as a mitogenic receptor for the lectins PHA, Con A and PWM. Strong, but unspecific inhibitory effects on lymphocyte stimulation are observed with unfractionated antisera and ascitic fluids. However, when purified IgG from these sources is used, no such effects are found, while at the same time, complete inhibition of ecto-5'-nucleotidase activity is maintained. It is concluded that the enzyme does not act as a mitogenic receptor for the lectins. When purine de novo synthesis of the lymphocytes is blocked by aminopterin and purine nucleotides in the extracellular medium are given as the only purine source, lymphocyte stimulation becomes dependent on the enzymatic activity of ecto-5'-nucleotidase. This is independent of the lectin used. Under these conditions, enzyme activity on the 20-30% 5'-nucleotidase-positive cells is necessary and is sufficient to support the stimulation of the whole culture. In these cultures, anti-5'-nucleotidase-IgG completely depresses cell proliferation, showing clearly that this is the only enzyme on the lymphocyte surface that is capable of degrading extracellular nucleotides.
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PMID:Is ecto-5'-nucleotidase essential for stimulation of human lymphocytes? Evidence against a role of the enzyme as mitogenic lectin receptor. 282 45

The activities of adenosine deaminase, purine nucleoside phosphorylase, membrane 5'-nucleotidase and DNA content in thymus and spleen lymphocytes as well as the immune function of T and B lymphocytes of the spleen of C3HA mice with o-AAT-induced hepatomas were studied 1, 3 weeks and 3, 8, 12 months after o-AAT treatment was instituted. In the early stages of the hepatocarcinogenesis (up to 3 months), the elevation of the activity of all the enzymes and DNA content in thymocytes and T and B lymphocytes was observed. These changes coincided with the enhancement of the immune responses that manifested in the increased content of PFC, EA-RFC and high response to PHA and Con A. In the late stages, the decreased activities of purine nucleosides and nucleotide metabolizing enzymes correlated with disturbances of lymphocyte differentiation and lowering of the host immune response.
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PMID:[Changes in purine metabolism and in the immune response in the thymic and splenic lymphocytes of C3HA mice during chemical hepatocarcinogenesis]. 633 63

An aqueous extract of normal human skin has been shown to contain an inhibitor of certain cell mediated immune reactions. In this report, the effect of the inhibitor on cell membrane markers and antibody dependent cellular cytotoxicity was determined. Significant diminution of E rosette formation was demonstrated using as little as 0.6 microgram of the skin fraction (p less than .02). Fc receptors for both IgG and IgM were reduced by 46-96% of controls in the presence of the skin inhibitor. On the other hand, no effect on the detection of the complement receptor or surface immunoglobulin was observed, indicating some specificity of binding. In addition, the antibody dependent cell-mediated cytotoxic reaction was inhibited on the skin extract. It was shown that the inhibitor interacted with the lymphocytes, not the antibody or target cells. No effect was detectable when the skin fraction was added after the interactions of effector cells, antibody, and target cells had occurred. This was in contrast to PHA-induced cytotoxicity which could be inhibited following the preincubation of the lymphocytes with the mitogen. Thus there appears to be 2 mechanisms by which the skin fraction interferes with cellular responses: inhibition of antibody binding to Fc receptors, and interference with a step in cellular activation following mitogen stimulation. Analysis of the extract showed the inhibitor was inactivated by trypsin, and did not contain sialic acid, 5'-nucleotidase of beta-N-acetylglucosaminidase, and thus was not associated with membrane or lysosomal enzymes.
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PMID:Inhibition of cell-mediated immune reactions by an aqueous extract of normal human skin. 710 62

The specific activity of phosphatidylinositol 4,5-bisphosphate phospholipase C (PIP2-PLC) and inositol 1,4,5-trisphosphate monophosphatase (IP3-MP) involved in phosphoinositide catabolism was found to be significantly lower in the total homogenate of four human lymphoblastoid cell lines, HSB-2, MOLT-4, CEM and JURKAT, than in resting and activated peripheral blood mononuclear cells, ranging from 0.8 to 3.2 and from 1.3 to 3.7 nmol/min/mg for PIP2-PLC and IP3-MP, respectively. In PHA-stimulated cells, the specific activities were enhanced 25 and 35% respectively over the values (8.02 and 7.83 nmol/min/mg, respectively) measured in resting peripheral blood mononuclear cells. After centrifugation on discontinuous sucrose gradient of cell homogenate, PIP2-PLC and IP3-MP activities were found to be predominantly associated with the cytosol fraction (> 69%) in HSB-2 and MOLT-4 cells, with a distribution similar to that found in PHA-stimulated and in resting lymphocytes. In CEM cells, about half of the total activity remained in this fraction, while in JURKAT lymphoblastic cells more than 45% of the total activity was recovered in the high-density membrane fraction (d = 1.20-1.25), the soluble PIP2-PLC and IP3-MP activity accounting for only 13 and 25%, respectively. Conversely, in less differentiated leukemic cells HSB-2 and MOLT-4, conspicuous activity of the ectoenzymes 5'-nucleotidase (5'-NT) and gamma-glutamyltransferase (gamma-GT) was recovered in the soluble fraction. Growing leukemic cells at a distinct level of differentiation have a general reduction in activity but a characteristic distribution of enzymes involved in the transmission of signals usually targeting the cell surface.
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PMID:Subcellular localization of inositide enzymes in established T-cell lines and activated lymphocytes. 809 39

The antiviral activity of azidothymidine (AZT), dideoxycytidine (ddC), and dideoxyinosine (ddI) against HIV-1 was comparatively evaluated in PHA-stimulated PBM. The mean drug concentration which yielded 50% p24 Gag negative cultures were substantially different: 0.06, 0.2, and 6 microM for AZT, ddC, and ddI, respectively. We found that AZT was preferentially phosphorylated to its triphosphate (TP) form in PHA-PBM rather than unstimulated, resting PBM (R-PBM), producing 10- to 17-fold higher ratios of AZTTP/dTTP in PHA-PBM than in R-PBM. The phosphorylation of ddC and ddI to their TP forms was, however, much less efficient in PHA-PBM, resulting in approximately 5-fold and approximately 15-fold lower ratios of ddCTP/dCTP and ddATP/dATP, respectively, in PHA-PBM than in R-PBM. The comparative order of PHA-induced increase in cellular enzyme activities examined was: thymidine kinase > uridine kinase > deoxycytidine kinase > adenosine kinase > 5'-nucleotidase. We conclude that AZT, ddC, and ddI exert disproportionate antiviral effects depending on the activation state of the target cells, i.e., ddI and ddC exert antiviral activity more favorably in resting cells than in activated cells, while AZT preferentially protects activated cells against HIV infection. Considering that HIV-1 proviral DNA synthesis in resting lymphocytes is reportedly initiated at levels comparable with those of activated lymphocytes, the current data should have practical relevance in the design of anti-HIV chemotherapy, particularly combination chemotherapy.
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PMID:Differential phosphorylation of azidothymidine, dideoxycytidine, and dideoxyinosine in resting and activated peripheral blood mononuclear cells. 838 46

The human leukocyte surface Ag CD38 was recently identified as a nicotinamide adenine dinucleotide (NAD)(+)-glycohydrolase ecto-enzyme, degrading NAD into nicotinamide and ADP-ribose. We show here that expression of CD38 is increased in the Jurkat T cell line after treatment with agents that augment intracellular cAMP, with the permeant cAMP analogue dibutyryl-cAMP (db-cAMP), and also with PMA, which activates protein kinase C. Treatment of human PBL T cells with db-cAMP or submitogenic doses of PMA also increased CD38 expression. Two other nucleotide-hydrolyzing activities were induced on the T cell surface concomitantly with CD38: the human PC-1 molecule, a nucleotide phosphodiesterase/pyrophosphatase that produces AMP from NAD or ADP-ribose, and a nucleotidase that produces adenosine from AMP, but which may be distinct from the CD73 5'-nucleotidase. All three enzymes were up-regulated after stimulation of human peripheral blood T cells with PHA. The coordinated regulation of these ecto-enzymes suggested that, besides a possible signaling function, they may recycle extracellular NAD by degrading it to adenosine and nicotinamide, which can be taken up by cells. In support of this hypothesis, db-cAMP-treated Jurkat cells could degrade extracellular NAD for de novo synthesis of purines, while untreated cells could not. Activated lymphocytes are often located in tissues in which cell death is common. It is suggested that the coordinated expression of these enzymes may allow activated T cells to re-use NAD and nucleotides from dead cells.
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PMID:Coordinated regulation in human T cells of nucleotide-hydrolyzing ecto-enzymatic activities, including CD38 and PC-1. Possible role in the recycling of nicotinamide adenine dinucleotide metabolites. 875 17