Adenosine inhibits and potentiates IgE‐dependent histamine release from human basophils by an A<sub>2</sub>‐receptor mediated mechanism

Church, Martin K.; Holgate, Stephen T.; Hughes, Philip

doi:10.1111/j.1476-5381.1983.tb10063.x

Cited by 103 publications

(35 citation statements)

References 21 publications

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“…The cause of this discrepancy is, again, not absolutely identifiable but is most likely a result ofthe different species oforigin ofthe neutrophils studied. Similar species differences have been well documented for the effects ofadenosine on stimulated mast cell or basophil function (31)(32)(33)(34). Our observation that 2-chloroadenosine inhibits stimulated neutrophil adherence to endothelial cells is important because neutrophil adherence is a critical first step for both endothelial cell injury (2, 5, 18, 35) and emigration of neutrophils from the vasculature (36).…”

Section: Introductionmentioning

confidence: 77%

Adenosine: an endogenous inhibitor of neutrophil-mediated injury to endothelial cells.

Cronstein¹,

Levin²,

Belanoff³

et al. 1986

J. Clin. Invest.

399

163

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Since adenosine and its analogue 2-chloroadenosine prevent neutrophils from generating superoxide anion in response to chemoattractants, we sought to determine whether these agents could inhibit neutrophil-mediated hnjury of endothelial cells. The chemoattractant N-formyl-methionyl-leucyl-phenylalanine (FMLP, 0.1 ,uM) enhanced the adherence of neutrophils to endothelial cells twofold (18±2% vs. 39±3% adherence, P < 0.001) and caused substantial neutrophil-mediated injury to endothelial cells (2±2% vs. 39±4% cytotoxicity, P < 0.001). 2-Chloroadenosine (10 ,uM) not only inhibited the adherence of stimulated neutrophils by 60% (24±2% adherence, P < 0.001) but also diminished the cytotoxicity by 51% (20±4% cytotoxicity, P <0.002). Furthermore, depletion of endogenously released adenosine from the medium by adenosine deaminase-enhanced injury to endothelial cells by stimulated neutrophils (from 39±4% to 69±3% cytotoxicity, P < 0.001). Indeed, in the presence of adenosine deaminase, even unstimulated neutrophils injured endothelial cells (19±4% vs. 2±2% cytotoxicity, P < 0.001). These data indicate that engagement of adenosine receptors prevents both the adhesion of neutrophils and the injury they cause to endothelial cells. Adenosine inhibits injury provoked not only by cells that have been stimulated by chemoattractants but also by unstimulated cells. Based on this model of acute vascular damage we suggest that adenosine is not only a potent vasodilator, but plays the additional role of protecting vascular endothelium from damage by neutrophils.

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Section: Introductionmentioning

confidence: 77%

Adenosine: an endogenous inhibitor of neutrophil-mediated injury to endothelial cells.

Cronstein¹,

Levin²,

Belanoff³

et al. 1986

J. Clin. Invest.

399

163

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“…Current research supports that activation of adenosine receptors potentiates mast cell mediator release after being induced by allergen challenge (Church et al, 1983;Fozard and Hannon, 2000;Meade et al, 2001). Activation of the A 1 adenosine receptor has been shown to cause bronchoconstriction in rabbit airway smooth muscle (Ali et al, 1994).…”

mentioning

confidence: 91%

Involvement of Mast Cells in Adenosine-Mediated Bronchoconstriction and Inflammation in an Allergic Mouse Model

Oldenburg

Mustafa

2004

J Pharmacol Exp Ther

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In allergen-induced asthma, activation of lung mast cells leads to bronchial constriction, increased mucus secretion, and an increase in the localization of inflammatory cells to the airways. The purpose of this study was to explore the role of mast cells in adenosine-mediated airway reactivity and inflammation using the mast cell degranulating agent, compound 48/80 (C48/80). Mice were sensitized and challenged with ragweed (or 0.9% saline) followed by C48/80 administration twice a day in increasing doses for 5 days. Dose-responsiveness to the nonspecific adenosine receptor agonist 5Ј-N-ethylcarboxamidoadenosine (NECA) was established, and lung lavage was performed 24 h later for cell differential analysis to evaluate inflammation. At a dose of 375 g/ml (aerosolized NECA), C48/80 pretreatment resulted in a significant attenuation in airway reactivity when compared with sensitized control mice (330.07 versus 581.57%, respectively). Lung lavage from the C48/80 treated mice showed a decrease in eosinophils (17.7 versus 60.9%, respectively) and an increase in macrophages when compared with the sensitized control group (76.4 versus 30.8%, respectively). These results support the conclusion that mast cell degranulation plays an important role in adenosine receptor-mediated airway hyperresponsiveness and inflammation.

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“…Millimolar concentrations of adenosine may also act at an intracellular purine site with a resultant inhibition of adenylate cyclase [4,5], In studies with human basophils, adenosine elevates cyclic AMP via an A2 adenosine receptor-mediated mechanism and in-hibits histamine release [6][7][8]. In contrast, adenosine po tentiates mediator secretion from rat peritoneal mast cells [9,10].…”

Section: Introductionmentioning

confidence: 99%

Effects of Adenosine on Histamine Release from Human Lung Fragments

Ott

Klotz

Vogt-Moykopf³

et al. 1992

Int Arch Allergy Immunol

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The actions of adenosine on histamine release of human lung fragments were investigated. Histamine release was stimulated either with the calcium ionophore A 23187 or with concanavalin A. Adenosine and its analogue 5′-N-ethyl-carboxamidoadenosine alone had no significant effect on basal release or on the release elicited by A 23187 or concanavalin A. However, in the presence of the adenosine receptor antagonist 8-[4-[[[[(2-aminoethyl)amino]-carbonyl] methyloxy]-phenyl]-1,3-dipropylaxanthine (XAC), which itself did not affect the release, adenosine increased the stimulated histamine release. On the other hand, in the presence of the nucleoside transport inhibitor S-(p-nitro-benzyl)-6-thioninosine (NBTI), adenosine caused a reduction in stimulated histamine release. NBTI itself caused a stimulation of release. Thus, a stimulatory effect of adenosine was seen in the presence of XAC, whereas an inhibitory effect was unmasked by NBTI. From these data it is concluded that adenosine exerts two opposing effects on histamine release in the human lung which neutralize each other: it inhibits release via a site antagonized by XAC, which presumably represents an A₂ adenosine receptor, and it stimulates release via a mechanism that is blocked by NBTI, suggesting that adenosine needs to reach the interior of cells to exert this effect. The slight stimulatory effect of NBTI alone demonstrates that trapping intracellularly formed adenosine inside mast cells leads to sufficient concentrations of adenosine to stimulate histamine release. These findings suggest an important bimodal role of adenosine in regulating histamine release in the human lung.

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Adenosine inhibits and potentiates IgE‐dependent histamine release from human basophils by an A₂‐receptor mediated mechanism

Cited by 103 publications

References 21 publications

Adenosine: an endogenous inhibitor of neutrophil-mediated injury to endothelial cells.

Adenosine: an endogenous inhibitor of neutrophil-mediated injury to endothelial cells.

Involvement of Mast Cells in Adenosine-Mediated Bronchoconstriction and Inflammation in an Allergic Mouse Model

Effects of Adenosine on Histamine Release from Human Lung Fragments

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Adenosine inhibits and potentiates IgE‐dependent histamine release from human basophils by an A2‐receptor mediated mechanism

Cited by 103 publications

References 21 publications

Adenosine: an endogenous inhibitor of neutrophil-mediated injury to endothelial cells.

Adenosine: an endogenous inhibitor of neutrophil-mediated injury to endothelial cells.

Involvement of Mast Cells in Adenosine-Mediated Bronchoconstriction and Inflammation in an Allergic Mouse Model

Effects of Adenosine on Histamine Release from Human Lung Fragments

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Adenosine inhibits and potentiates IgE‐dependent histamine release from human basophils by an A₂‐receptor mediated mechanism