CD39/NTPDase-1 activity and expression in normal leukocytes

Pulte, E. Dianne; Broekman, M. Johan; Olson, Kim E.; Drosopoulos, Joan H.F.; Kizer, Jorge R.; Islam, Naziba; Marcus, Aaron J.

doi:10.1016/j.thromres.2007.04.008

Cited by 88 publications

(89 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…40 The ex vivo expression levels of these molecules by Tregs are shown in Figure 4. As in previous studies, 41 there was individual variability in the expression of these molecules in the three groups and no significant differences among them were found, although T2R patients showed a trend for lower expression of CTLA-4 and FoxP3. We also assessed the in vitro expression of these molecules in unstimulated and MLCwA and PHA-stimulated Tregs (Table 1).…”

Section: Resultssupporting

confidence: 68%

Development of Type 2, But Not Type 1, Leprosy Reactions is Associated with a Severe Reduction of Circulating and In situ Regulatory T-Cells

Vieira¹,

Trindade²,

Pagliari³

et al. 2016

The American Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

Abstract. Leprosy is frequently complicated by the appearance of reactions that are difficult to treat and are the main cause of sequelae. We speculated that disturbances in regulatory T-cells (Tregs) could play a role in leprosy reactions. We determined the frequency of circulating Tregs in patients with type 1 reaction (T1R) and type 2 reaction (T2R). The in situ frequency of Tregs and interleukin (IL)-17, IL-6, and transforming growth factor beta (TGF)-β-expressing cells was also determined. T2R patients showed markedly lower number of circulating and in situ Tregs than T1R patients and controls. This decrease was paralleled by increased in situ IL-17 expression but decreased TGF-β expression. Biopsies from T1R and T2R patients before the reaction episodes showed similar number of forkhead box protein P3 + (FoxP3+) and IL-17+ cells. However, in biopsies taken during the reaction, T2R patients showed a decrease in Tregs and increase in IL-17+ cells, whereas T1R patients showed the opposite: Tregs increased but IL-17+ cells decreased. We also found decreased expansion of Tregs upon in vitro stimulation with Mycobacterium leprae and a trend for lower expression of FoxP3 and the immunosuppressive molecule cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in T2R Tregs. Our results provide some evidence to the hypothesis that, in T2R, downmodulation of Tregs may favor the development of T-helper-17 responses that characterize this reaction.

show abstract

Section: Resultssupporting

confidence: 68%

Development of Type 2, But Not Type 1, Leprosy Reactions is Associated with a Severe Reduction of Circulating and In situ Regulatory T-Cells

Vieira¹,

Trindade²,

Pagliari³

et al. 2016

The American Society of Tropical Medicine and Hygiene

View full text Add to dashboard Cite

show abstract

“…The levels for NO secretion found in these two situations were similar, indicating that ATP enzymatic hydrolysis was not decisive for NO release. However, CD39/NTPDase 1 is expressed on numerous different types of normal leukocytes, including neutrophils [40]. In this study, we could not neglect the nucleotide hydrolysis by the neutrophil NTPDase considering that NTPDase1 efficiently hydrolyzes ATP.…”

Section: Discussionmentioning

confidence: 99%

Involvement of purinergic signaling on nitric oxide production by neutrophils stimulated with Trichomonas vaginalis

Frasson

Carli

Bonan

et al. 2011

Purinergic Signalling

View full text Add to dashboard Cite

Trichomonas vaginalis is a parasite from the human urogenital tract that causes trichomonosis, the most prevalent non-viral sexually transmitted disease. The neutrophil infiltration has been considered to be primarily responsible for cytological changes observed at infection site, and the chemoattractants can play an important role in this leukocytic recruitment. Nitric oxide (NO) is one of the most widespread mediator compounds, and it is implicated in modulation of immunological mechanisms. Extracellular nucleotides and nucleosides are signaling molecules involved in several processes, including immune responses and control of leukocyte trafficking. Ectonucleoside triphosphate diphosphohydrolase members, ecto-5′-nucleotidase, and adenosine deaminase (ectoADA) have been characterized in T. vaginalis. Herein, we investigated the effects of purinergic system on NO production by neutrophils stimulated with T. vaginalis. The trophozoites were able to induce a high NO synthesis by neutrophils through iNOS pathway. The extracellular nucleotides ATP, ADP, and ATPγS (a nonhydrolyzable ATP analog) showed no significant change in NO secretion. In contrast, adenosine and its degradation product, inosine, promoted a low production of the compound. The immunosuppressive effect of adenosine upon NO release by neutrophils occurred due to adenosine A 2A receptor activation. The ecto-5′-nucleotidase activity displayed by T. vaginalis was shown to be important in adenosine generation, indicating the efficiency of purinergic cascade. Our data suggest the influence of purinergic signaling, specifically adenosinergic system, on NO production by neutrophils in T. vaginalis infection, contributing to the immunological aspects of disease.

show abstract

“…An additional variable is represented by the levels of ectonucleotidases, which rapidly hydrolyze the released ATP (32,33), thereby limiting IL-1␤ secretion, as confirmed by the strong increase in ATP and IL-1␤ in culture fluids when monocytes stimulations are carried out in the presence of ecto-ATPase inhibitors. Ecto-nucleotidases are expressed not only by monocytes (38), but also by parasites and bacteria (39), possibly representing an escape mechanism evolved by pathogens to limit the inflammatory response. Even in the presence of ATPase inhibitors, the ATP measured in monocytes culture fluids is well below the threshold required to stimulate P2X 7 R. This discrepancy has been found also in other experimental systems [astrocytes (32) and renal glomeruli (33)], where the ATP levels measured in extracellular media significantly underestimate the amount of ATP actually released at the cell surface, because of the fast diffusion and the rapid hydrolysis of the cell-derived ATP (32,33).…”

Section: Discussionmentioning

confidence: 99%

ATP is released by monocytes stimulated with pathogen-sensing receptor ligands and induces IL-1β and IL-18 secretion in an autocrine way

Piccini¹,

Carta²,

Tassi³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

430

394

View full text Add to dashboard Cite

IL-1␤ and IL-18 are crucial mediators of inflammation, and a defective control of their release may cause serious diseases. Yet, the mechanisms regulating IL-1␤ and IL-18 secretion are partially undefined. Both cytokines are produced as inactive cytoplasmic precursors. Processing to the active form is mediated by caspase-1, which is in turn activated by the multiprotein complex inflammasome. Here, we show that in primary human monocytes microbial components acting on different pathogen-sensing receptors and the danger-associated molecule uric acid are all competent to induce maturation and secretion of IL-1␤ and IL-18 through a process that involves as a first event the extracellular release of endogenous ATP. ATP release is followed by autocrine stimulation of the purinergic receptors P2X 7. Indeed, antagonists of the P2X7 receptor (P2X7R), or treatment with apyrase, prevent IL-1␤ and IL-18 maturation and secretion triggered by the different stimuli. At variance, blocking P2X 7R activity has no effects on IL-1␤ secretion by monocytes carrying a mutated inflammasome that does not require exogenous ATP for activation. P2X 7R engagement is followed by K ؉ efflux and activation of phospholipase A2. Both events are required for processing and secretion induced by all of the stimuli. Thus, stimuli acting on different pathogen-sensing receptors converge on a common pathway where ATP externalization is the first step in the cascade of events leading to inflammasome activation and IL-1␤ and IL-18 secretion.inflammation ͉ nonclassical secretion ͉ pathogen-associated molecular patterns ͉ processing

show abstract

CD39/NTPDase-1 activity and expression in normal leukocytes

Abstract: We conclude that CD39 activity and expression are present to varying degrees on all leukocytes types examined. Differences between leukocyte types should be considered when examining CD39 in disease states.

Cited by 88 publications

References 30 publications

Development of Type 2, But Not Type 1, Leprosy Reactions is Associated with a Severe Reduction of Circulating and In situ Regulatory T-Cells

Development of Type 2, But Not Type 1, Leprosy Reactions is Associated with a Severe Reduction of Circulating and In situ Regulatory T-Cells

Involvement of purinergic signaling on nitric oxide production by neutrophils stimulated with Trichomonas vaginalis

ATP is released by monocytes stimulated with pathogen-sensing receptor ligands and induces IL-1β and IL-18 secretion in an autocrine way

Contact Info

Product

Resources

About