Characterization of NTPDase (NTPDase1; ecto-apyrase; ecto-diphosphohydrolase; CD39; EC 3.6.1.5) activity in human lymphocytes

Leal, Daniela Bitencourt Rosa; Streher, Cristiane A.; Neu, Tiago N.; Bittencourt, Fábio P.; Leal, Cláudio A.M.; Silva, José E.P. da; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina

doi:10.1016/j.bbagen.2004.09.006

Cited by 128 publications

(90 citation statements)

References 38 publications

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“…However, whether such CD39-bearing virions originate from CD4 + T lymphocytes or macrophages remains unclear, as this ectoenzyme is expressed in both cell types. 42 Previous studies indicate that only 2-3% of T cells express CD39, 43 but this percentage increases sharply following T cell activation. 42 The CD4-expressing T cells present in both PHA-activated PBMCs and tonsil histocultures are mostly in an activated state, suggesting that CD39-bearing viruses are probably originating from this cell type.…”

Section: Discussionmentioning

confidence: 99%

“…33,34 The CD39 molecule is expressed in quiescent endothelial cells, activated B cells, natural killer (NK) cells and subsets of T cells, as well as in macrophages and dendritic cells. [35][36][37][38][39][40][41][42][43] Initially described as a modulator of homotypic adhesion in B cells, 42,44 CD39 is now recognized as the dominant vascular NTPDase and a critical thromboregulatory molecule. 25,27,45 It is actually the major ectonucleotidase responsible for the hydrolysis of nucleotides in the blood.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

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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“…In the past decade, additional enzymes with high homology to NTPDase1 were sequenced (66), which required reassessment of azide specificity. Recent studies showed that azide inhibits NTPDase1 (42) and NTPDase3 (72), but not the other surface NTPDases (26,71), NSAP (30) or NPPs (69). Therefore, this inhibitor would target specifically NTPDase1 and NTPDase3 on human airway epithelia.…”

Section: Contribution Of the Azide-sensitive Ntpdasesmentioning

confidence: 99%

“…For instance, NTPDase1 is considered a low-capacity, high-affinity ectonucleotidase [K m ϭ 10 -20 M (11)], whereas NTPDase3 falls in the high-capacity, low-affinity category regulating higher nucleotide concentrations [K m ϭ 90 -130 M (72)]. We recently reported a strong sensitivity of nucleotide metabolism to azide on HBE cultures (Ͼ40%) (8), supporting a major role for NTPDase1 (42) and/or NTPDase3 (72), but not the other surface NTPDases (26,71), NSAP (30), or NPPs (69). Human NTPDase1 has been extensively investigated and assigned critical roles in the prevention of ischemia-reperfusion injury (31) and transplant rejection (2,67), in thrombus formation, and inflammatory responses (6,20).…”

mentioning

confidence: 99%

Cystic fibrosis remodels the regulation of purinergic signaling by NTPDase1 (CD39) and NTPDase3

Fausther

Pelletier

Ribeiro

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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Airway defenses are regulated by a complex purinergic signaling network located on the epithelial surfaces, where ATP stimulates the clearance of mucin and pathogens. The present study shows that the obstructive disease cystic fibrosis (CF) affects the activity, expression, and tissue distribution of two ectonucleotidases found critical for the regulation of ATP on airway surfaces: NTPDase1 and NTPDase3. Functional polarities and mRNA expression levels were determined on primary cultures of human bronchial epithelial (HBE) cells from healthy donors and CF patients. The in vitro model of the disease was completed by exposing CF HBE cultures for 4 days to supernatant of the mucopurulent material (SMM) collected from the airways of CF patients. We report that NTPDase1 and NTPDase3 are coexpressed on HBE cultures, where they regulate physiological and excess nucleotide concentrations, respectively. In aseptic conditions, CF epithelia exhibit >50% lower NTPDase1 activity, protein, and mRNA levels than normal epithelia, whereas these parameters are threefold higher for NTPDase3. Exposure to SMM induced opposite polarity shifts of the two NTPDases on both normal and CF epithelia, apical NTPDase1 being mobilized to basolateral surfaces and bilateral NTPDase3 to the apical surface. Their immunolocalization in human tissue revealed that NTPDase1 is expressed in epithelial, inflammatory, and endothelial cells, whereas NTPDase3 is restricted to epithelial cells. Furthermore, the SMM-exposed CF HBE cultures reproduced the impact of the disease on their in vivo distribution. This study provides evidence that an extensive remodeling of the enzymatic network regulating clearance occurs in the airways of CF patients.

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“…CD39 is an integral membrane protein that metabolizes extracellular adenosine triphosphate (ATP) and adenosine diphosphate (ADP) to adenosine monophosphate (11)(12)(13). Previous studies demonstrated that CD39 is expressed in numerous cells, including leukocytes (14,15), Treg cells (16,17) and endothelial cells (18). CD39 dysregulation has been associated with multiple human cancer types, including leukemia (19), colon cancer (20) and pancreatic cancer (21).…”

Section: Introductionmentioning

confidence: 99%

High expression of CD39 in gastric cancer reduces patient outcome following radical resection

Cai

Wang

et al. 2016

Oncology Letters

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Abstract. Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1), also known as cluster of differentiation (CD)39, is the rate-limiting enzyme in the generation of immunosuppressive adenosine and is important in tumor progression. The present study evaluated the expression of CD39 + and CD39 + forkhead box P3 (FoxP3) + regulatory T (Treg) cells in gastric cancer (GC), and determined their prognostic roles in patients with GC following radical resection. It was observed that CD39 was expressed at significantly higher rates in tumor tissues as compared with paired peritumoral tissues. Overexpression of tumor CD39 was correlated with overall survival (OS). Furthermore, CD39 expression in GC tissues exhibited a prognostic role in OS. The CD39 + FoxP3 + /FoxP3 + ratio in tumor tissues was higher than that in paired peritumoral tissues, and CD39 + FoxP3 + Treg cells were a better prognostic indicator than FoxP3 + Treg cells for OS. Collectively, our study indicates that overexpression of CD39 in GC is a predictor of poor outcome for GC patients following radical resection. CD39 + FoxP3 + Treg cells are a potential target for cancer immunotherapy.

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Characterization of NTPDase (NTPDase1; ecto-apyrase; ecto-diphosphohydrolase; CD39; EC 3.6.1.5) activity in human lymphocytes

Cited by 128 publications

References 38 publications

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

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

Cystic fibrosis remodels the regulation of purinergic signaling by NTPDase1 (CD39) and NTPDase3

High expression of CD39 in gastric cancer reduces patient outcome following radical resection

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