Ecto‐ATPase: an activation marker necessary for effector cell function

Dombrowski, Kenneth E.; Ke, Yinghai; Brewer, Kenneth A; Kopp, Judith A.

doi:10.1111/j.1600-065x.1998.tb01575.x

Cited by 72 publications

(47 citation statements)

References 38 publications

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“…Enzymes whose catalytic site faces the extracellular space offer a great therapeutic opportunity (Figs 2 and 3) [38]. In this context, ectoenzymes are attractive candidates for designing new approaches to interfere with pathological events, such as leukocyte trafficking [110].…”

Section: Discussionmentioning

confidence: 99%

“…Koziak et al [73] observed a correlation between the levels of CD39 expression and NTPDase activity in human NK cells. Furthermore, E-NTPDases may also exert extra-enzymatic functions in that CD39 has been proposed to be a cell-surface signaling molecule playing a role in the regulation of effector functions of activated lymphocytes [38].…”

Section: Immunomodulation and Cell-cell Interactionsmentioning

confidence: 99%

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NTPDase and 5'‐nucleotidase activities in physiological and disease conditions: New perspectives for human health

et al. 2007

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Abstract. Extracellular nucleotides and nucleosides act as signaling molecules involved in a wide spectrum of biological effects. Their levels are controlled by a complex cell surface-located group of enzymes called ectonucleotidases. There are four major families of ectonucleotidases, nucleoside triphosphate diphosphohydrolases (NTPDases/CD39), ectonucleotide pyrophosphatase/phosphodiesterases (E-NPPs), alkaline phosphatases and ecto-5'-nucleotidase. In the last few years, substantial progress has been made toward the molecular identification of members of the ectonucleotidase families and their enzyme structures and functions. In this review, there is an emphasis on the involvement of NTPDase and 5'-nucleotidase activities in disease processes in several tissues and cell types. Brief background information is given about the general characteristics of these enzymes, followed by a discussion of their roles in thromboregulatory events in diabetes, hypertension, hypercholesterolemia and cancer, as well as in pathological conditions where platelets are less responsive, such as in chronic renal failure. In addition, immunomodulation and cell-cell interactions involving these enzymes are considered, as well as ATP and ADP hydrolysis under different clinical conditions related with alterations in the immune system, such as acute lymphoblastic leukemia (ALL), Bchronic lymphocytic leukemia (B-CLL) and infections associated with human immunodeficiency virus (HIV). Finally, changes in ATP, ADP and AMP hydrolysis induced by inborn errors of metabolism, seizures and epilepsy are discussed in order to highlight the importance of these enzymes in the control of neuronal activity in pathological conditions. Despite advances made toward understanding the molecular structure of ectonucleotidases, much more investigation will be necessary to entirely grasp their role in physiological and pathological conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Immunomodulation and Cell-cell Interactionsmentioning

confidence: 99%

NTPDase and 5'‐nucleotidase activities in physiological and disease conditions: New perspectives for human health

et al. 2007

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“…68 Hydrolysis of extracellular ATP by ecto-ATPases has been shown to be essential for activation and proliferation of lymphocytes. 69 In addition, hydrolysis of extracellular ATP is considered as an essential step in calcium mobilization mediated by T cell receptor and Fc-gamma receptor signalling in cytotoxic T lymphocytes and NK cells. 70,71 These observations suggest that ecto-ATPase has an obligatory role in calcium influx and hence in many effector functions of T, B and NK cells.…”

Section: Discussionmentioning

confidence: 99%

The Nucleoside Triphosphate Diphosphohydrolase-1/CD39 Is Incorporated into Human Immunodeficiency Type 1 Particles, Where It Remains Biologically Active

Barat

Martin

Beaudoin

et al. 2007

Journal of Molecular Biology

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Human immunodeficiency virus type 1 (HIV-1) carries a variety of host proteins in addition to virus-encoded structural proteins, both in its envelope and inside the viral particle. Previous studies have reported that the HIV-1 life-cycle is affected by such virus-associated host cell surface proteins. The nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), also known as CD39, is a plasma membrane-bound ectoenzyme that hydrolyzes extracellular ATP and ADP to AMP. It has been shown that CD39 inhibits platelet function, and is thus a critical thromboregulatory molecule. We demonstrate here that host-derived CD39 is acquired by both laboratory-adapted and clinical variants of HIV-1 produced in cellular reservoirs of the virus. Moreover, purified CD39-bearing virions, but not isogenic viruses lacking CD39, display strong ATPase and ADPase activities. It is of particular interest that virions bearing this cellular enzyme can inhibit ADP-induced platelet aggregation, an effect blocked by an NTPDase inhibitor. On the basis of published and the present data on the functionality of human cellular proteins embedded within HIV-1, it can be proposed that these proteins might contribute to some of the immunologic deficiencies seen in infected individuals.

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“…This progress is related to the finding that, in contrast to the established view, nucleotides can be found in significant concentrations outside cells (Gordon, 1986;Dombrowski et al, 1998). Nucleotides released to the extracellular medium may exert their effects on other cells in the vicinity of the secretion site and modulate biological processes, by binding to specific cell surface receptors (Dombrowski et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…During the past two decades, considerable progress has been achieved in the study of ectonucleotidases in general (Zimmermann, 1996) and ecto-ATPases in particular (Plesner, 1995;Dombrowski et al, 1998;Meyer-Fernandes, 2002). This progress is related to the finding that, in contrast to the established view, nucleotides can be found in significant concentrations outside cells (Gordon, 1986;Dombrowski et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Ecto-nucleotidase activities in the fat body ofRhodnius prolixus

Entringer

Gondim

Meyer‐Fernandes

2005

Arch. Insect Biochem. Physiol.

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In this study, we describe the ability of intact fat body of an insect, Rhodnius prolixus, to hydrolyze extracellular ATP. In these fat bodies, the ATP hydrolysis was low in the absence of any divalent metal, and was stimulated by MgCl 2 . Both activities (in the absence or presence of MgCl 2 ) were linear with time for at least 30 min. In order to confirm the observed nucleotidase activities as ecto-nucleotidases, we used an impermeant inhibitor, DIDS (4, 4′-diisothiocyanostylbene 2′-2′-disulfonic acid). This reagent inhibited both nucleotidase activities and its inhibitory effect was suppressed by ATP. Both ecto-nucleotidase activities were insensitive to inhibitors of other ATPase and phosphatase activities, such as oligomycin, sodium azide, bafilomycin, ouabain, vanadate, molybdate, sodium fluoride, levamizole, tartrate, p-NPP, sodium phosphate, and suramin. Concanavalin A, activator of some ecto-ATPases, was able to stimulate the Mg 2+ -independent nucleotidase activity, but not the Mg 2+ -dependent one. The Mg 2+ -independent nucleotidase activity was enhanced with increases in the pH in the range between 6.4-8.0, but the Mg 2+ -dependent nucleotidase activity was not affected. Besides MgCl 2 , the ecto-ATPase activity was also stimulated by CaCl 2 , MnCl 2 , and SrCl 2 , but not by ZnCl 2 . ATP, ADP, and AMP were the best substrates for the Mg 2+ -dependent ecto-nucleotidase activity, and CTP, GTP, and UTP produced very low reaction rates. However, the Mg 2+ -independent nucleotidase activity recognized all these nucleotides producing similar reaction rates, but GTP was a less efficient substrate. The possible role of the two ecto-nucleotidase activities present on the cell surface of fat body of Rhodnius prolixus, which are distinguished by their substrate specificity and their response to Mg 2+ , is discussed. Arch. Insect Biochem. Physiol. 61:1-9, 2006.

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Ecto‐ATPase: an activation marker necessary for effector cell function

Cited by 72 publications

References 38 publications

NTPDase and 5'‐nucleotidase activities in physiological and disease conditions: New perspectives for human health

NTPDase and 5'‐nucleotidase activities in physiological and disease conditions: New perspectives for human health

The Nucleoside Triphosphate Diphosphohydrolase-1/CD39 Is Incorporated into Human Immunodeficiency Type 1 Particles, Where It Remains Biologically Active

Ecto-nucleotidase activities in the fat body ofRhodnius prolixus

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