Endogenous adenosine regulates neutrophil pro-inflammatory activities by cyclic AMP-dependent accelerated clearance of cytosolic calcium

Theron, Annette J.; Steel, Helen C.; Tintinger, Gregory Ronald

doi:10.1007/pl00012434

Cited by 19 publications

(18 citation statements)

References 33 publications

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“…Because PGE 2 has no impact on the release of Ca 2ϩ from intracellular stores, the capacitive calcium entry is probably not affected by PGE 2 , and a relevant hypothesis is that PGE 2 rather inhibits the opening of a receptor-operated calcium channel (Ahmed et al, 1995). Another possibility is that, as shown previously for adenosine and other cAMP elevating agents, PGE 2 could promote an accelerated clearance of cytosolic calcium by up-regulating the endo-membrane Ca 2ϩ -ATPase that recaptures cytosolic calcium (Theron et al, 2002). However, this hypothesis would account in part for the decreased mobilization of calcium but not for the inhibition of Mn 2ϩ influx observed in the presence of PGE 2 .…”

Section: Discussionmentioning

confidence: 89%

Prostaglandin E2 Inhibits the Phospholipase D Pathway Stimulated by Formyl-methionyl-leucyl-phenylalanine in Human Neutrophils. Involvement of EP2 Receptors and Phosphatidylinositol 3-kinase γ

Burelout¹,

Thibault²,

Levasseur³

et al. 2004

Molecular Pharmacology

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Prostaglandin E 2 (PGE 2 ), originally discovered as a pro-inflammatory mediator, also inhibits several chemoattractant-elicited neutrophil functions, including adhesion, secretion of cytotoxic enzymes, production of superoxide anions, and chemotaxis. In this study, we have examined the effects of PGE 2 and prostaglandin E (EP) receptor-selective agonists/antagonists on several steps of the formyl-methionyl-leucyl-phenylalanine (fMLP)-induced phospholipase D (PLD) activation pathway in human neutrophils to elucidate the PGE 2 inhibitory mechanism. PGE 2 and EP 2 receptor agonists inhibited the stimulation of the activity of PLD induced by fMLP in a concentration-dependent manner. The fMLP-stimulated translocation to membranes of protein kinase C ␣, Rho, and Arf GTPases was diminished in the presence of PGE 2 or EP 2 agonists. Moreover, PGE 2 and EP 2 agonists decreased the activation of phosphatidylinositol 3-kinase ␥ (PI3K␥) and Tec kinases as well as the tyrosine phosphorylation of proteins stimulated by fMLP. These data provide strong evidence that 1) the inhibitory effects of PGE 2 on the fMLP-induced PLD activation pathway were mediated via EP 2 receptors and that 2) the suppression of PI3K␥ activity was the crucial step in the EP 2 -mediated inhibition of the fMLP-induced signaling cascade.

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Section: Discussionmentioning

confidence: 89%

Prostaglandin E2 Inhibits the Phospholipase D Pathway Stimulated by Formyl-methionyl-leucyl-phenylalanine in Human Neutrophils. Involvement of EP2 Receptors and Phosphatidylinositol 3-kinase γ

Burelout¹,

Thibault²,

Levasseur³

et al. 2004

Molecular Pharmacology

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“…In addition, adenosine can inhibit reactive nitrogen species and reactive oxygen species production by monocytes/macrophages [40] and can impede lymphocyte adhesion and attenuate the proliferative and cytotoxic responses of activated T cells [41], [42]. Extracellular adenosine has been shown to inhibit adhesion of neutrophils to vascular endothelial cells and, at higher concentrations, to induce apoptosis of promyelocytes [43], [44], [45]. Adenosine can inhibit the generation of reactive oxygen species and the oxidative burst by immunostimulated neutrophils, as well as inhibit neutrophil degranulation and the generation of several inflammatory mediators [46].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Schistosome Tegumental Alkaline Phosphatase (SmAP)

Bhardwaj

Skelly

2011

PLoS Negl Trop Dis

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Schistosomes are parasitic platyhelminths that currently infect over 200 million people globally. The parasites can live for years in a putatively hostile environment - the blood of vertebrates. We have hypothesized that the unusual schistosome tegument (outer-covering) plays a role in protecting parasites in the blood; by impeding host immunological signaling pathways we suggest that tegumental molecules help create an immunologically privileged environment for schistosomes. In this work, we clone and characterize a schistosome alkaline phosphatase (SmAP), a predicted ∼60 kDa glycoprotein that has high sequence conservation with members of the alkaline phosphatase protein family. The SmAP gene is most highly expressed in intravascular parasite life stages. Using immunofluorescence and immuno-electron microscopy, we confirm that SmAP is expressed at the host/parasite interface and in internal tissues. The ability of living parasites to cleave exogenous adenosine monophosphate (AMP) and generate adenosine is very largely abolished when SmAP gene expression is suppressed following RNAi treatment targeting the gene. These results lend support to the hypothesis that schistosome surface enzymes such as SmAP could dampen host immune responses against the parasites by generating immunosuppressants such as adenosine to promote their survival. This notion does not rule out other potential functions for the adenosine generated e.g. in parasite nutrition.

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“…The major cellular targets of PKA are Ca 2+ mobilization and clearance mechanisms,40–50 and regulation of the expression of genes encoding anti-inflammatory/proinflammatory proteins at both the transcriptional and translational levels 51–74. Epac1 also appears to modulate gene expression 75–77…”

Section: β2-adrenoceptor Agonists and Therapy Of Respiratory Airway Dmentioning

confidence: 99%

“…In this setting of restoration of Ca 2+ homeostasis to activated neutrophils, the autocrine interaction of adenosine with G-protein/adenylyl cyclase-coupled A2A receptors appears to be the primary mechanism for generation of cAMP,49,50 which is complemented by β2-agonists and PDE4 inhibitors 43…”

Section: β2-adrenoceptor Agonists and Therapy Of Respiratory Airway Dmentioning

confidence: 99%

Can the anti-inflammatory activities of β2-agonists be harnessed in the clinical setting?

Theron

Steel

Tintinger³

et al. 2013

DDDT

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Beta2-adrenoreceptor agonists (β2-agonists) are primarily bronchodilators, targeting airway smooth muscle and providing critical symptomatic relief in conditions such as bronchial asthma and chronic obstructive pulmonary disease. These agents also possess broad-spectrum, secondary, anti-inflammatory properties. These are mediated largely, though not exclusively, via interactions with adenylyl cyclase-coupled β2-adrenoreceptors on a range of immune and inflammatory cells involved in the immunopathogenesis of acute and chronic inflammatory disorders of the airways. The clinical relevance of the anti-inflammatory actions of β2-agonists, although often effective in the experimental setting, remains contentious. The primary objectives of the current review are: firstly, to assess the mechanisms, both molecular and cell-associated, that may limit the anti-inflammatory efficacy of β2-agonists; secondly, to evaluate pharmacological strategies, several of which are recent and innovative, that may overcome these limitations. These are preceded by a consideration of the various types of β2-agonists, their clinical applications, and spectrum of anti-inflammatory activities, particularly those involving adenosine 3′,5′-cyclic adenosine monophosphate-activated protein kinase-mediated clearance of cytosolic calcium, and altered gene expression in immune and inflammatory cells.

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Endogenous adenosine regulates neutrophil pro-inflammatory activities by cyclic AMP-dependent accelerated clearance of cytosolic calcium

Abstract: These results are compatible with a physiological role for adenosine in promoting deactivation of neutrophils, possibly by promoting cAMP-dependent clearance of Ca2+ from the cytosol of the cells by the endo-membrane Ca2+-ATPase.

Cited by 19 publications

References 33 publications

Prostaglandin E2 Inhibits the Phospholipase D Pathway Stimulated by Formyl-methionyl-leucyl-phenylalanine in Human Neutrophils. Involvement of EP2 Receptors and Phosphatidylinositol 3-kinase γ

Prostaglandin E2 Inhibits the Phospholipase D Pathway Stimulated by Formyl-methionyl-leucyl-phenylalanine in Human Neutrophils. Involvement of EP2 Receptors and Phosphatidylinositol 3-kinase γ

Characterization of Schistosome Tegumental Alkaline Phosphatase (SmAP)

Can the anti-inflammatory activities of β2-agonists be harnessed in the clinical setting?

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Endogenous adenosine regulates neutrophil pro-inflammatory activities by cyclic AMP-dependent accelerated clearance of cytosolic calcium

Abstract: These results are compatible with a physiological role for adenosine in promoting deactivation of neutrophils, possibly by promoting cAMP-dependent clearance of Ca2+ from the cytosol of the cells by the endo-membrane Ca2+-ATPase.

Cited by 19 publications

References 33 publications

Prostaglandin E2 Inhibits the Phospholipase D Pathway Stimulated by Formyl-methionyl-leucyl-phenylalanine in Human Neutrophils. Involvement of EP2 Receptors and Phosphatidylinositol 3-kinase γ

Prostaglandin E2 Inhibits the Phospholipase D Pathway Stimulated by Formyl-methionyl-leucyl-phenylalanine in Human Neutrophils. Involvement of EP2 Receptors and Phosphatidylinositol 3-kinase γ

Characterization of Schistosome Tegumental Alkaline Phosphatase (SmAP)

Can the anti-inflammatory activities of &beta;2-agonists be harnessed in the clinical setting?

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Can the anti-inflammatory activities of β2-agonists be harnessed in the clinical setting?