Protective Effect of 2-Chloroadenosine on Lung Ischemia Reperfusion Injury

Marts, Boyd C.; Baudendistel, Lawrence J.; Naunheim, Keith S.; Dahms, Thomas E.

doi:10.1006/jsre.1993.1081

Cited by 13 publications

(4 citation statements)

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“…In contrast, in the kidney, the highly selective A 3 AR agonist IB‐MECA worsened renal IR injury (7). Previous studies reported that A 2 AR agonist and A 1 AR antagonist blocked IR‐induced lung injury (5,6,41,42). The present results expand these previous observations and elucidate the role of A 3 AR.…”

Section: Discussionmentioning

confidence: 90%

Activation of A3 Adenosine Receptor Provides Lung Protection Against Ischemia-Reperfusion Injury Associated with Reduction in Apoptosis

Rivo

Zeira

Galun

et al. 2004

American Journal of Transplantation

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Apoptosis has been described in various models of ischemia-reperfusion (IR) injury, including lung transplantation. A 3 adenosine receptor (AR) has been linked to a variety of apoptotic processes. The effect of A 3 AR activation on lung injury and apoptosis, following IR, has not been reported to date. In a spontaneously breathing cat model, in which the left lower lobe of the lung was isolated and subjected to 2 h of ischemia and 3 h of reperfusion, we tested the effect of IB-MECA, a selective A 3 AR agonist, on lung apoptosis and injury. Significant increase in the extent of apoptosis was observed following lung reperfusion. IB-MECA, administered before IR, and before or with reperfusion, markedly (p < 0.01) attenuated indices of injury and apoptosis including the percentage of injured alveoli, wet/dry weight ratio, myeloperoxidase activity, in situ terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate nick end-labeling (TUNEL) positive cells, and caspase 3 activity and expression. The protective effects of IB-MECA were completely blocked by pretreatment with the selective A 3 AR antagonist MRS-1191. In summary, even when given after the onset of ischemia, the A 3 AR agonist IB-MECA conferred a powerful protection against reperfusion lung injury, which was associated with decreased apoptosis. This suggests a potentially important role for A 3 AR in lung IR injury.

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Section: Discussionmentioning

confidence: 90%

Activation of A3 Adenosine Receptor Provides Lung Protection Against Ischemia-Reperfusion Injury Associated with Reduction in Apoptosis

Rivo

Zeira

Galun

et al. 2004

American Journal of Transplantation

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“…For example, activation of A 2A receptors seems to be associated with inhibition of tumour necrosis factor (TNF)‐α, IL‐6 and IL‐8 release by activated mononuclear phagocytes. TNF‐α and other cytokines are important in the pathogenesis of sepsis (Fong & Lowry, 1990) and ischemia‐reperfusion injury (Seekamp et al ., 1993) and the well‐established beneficial effects of adenosine on ischemia‐reperfusion injury have been attributed mainly to direct inhibition of neutrophil function (Marts et al ., 1993). The antiinflammatory effects of adenosine and its receptor analogues were first suggested in 1983 when Cronstein et al .…”

Section: Introductionmentioning

confidence: 99%

A_2A adenosine receptors in human peripheral blood cells

Gessi

Varani

Merighi

et al. 2000

British J Pharmacology

152

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“…In lymphocytes, adenosine inhibits the synthesis of immunoglobulins (Moroz & Stevens, 1980) and lymphocyte-mediated cytolysis (Wolberg et al, 1975). Recent in vivo studies have demonstrated a protective role of adenosine and its structural analogues in models of acute inflammation such as experimental adjuvant arthritis (Green et al, 1991), ischaemia-reperfusion (Grisham et al, 1989;Kaminski & Proctor, 1989;Forman et al, 1993;Marts et al, 1993) and carregeenin-induced pleural inflammation (Schrier et al, 1990). Furthermore, methotrexate, an antifolate commonly used in the treatment of rheumatoid arthritis patients, causes accumulation of adenosine and inhibition of leukocyte migration in inflammatory exudates in mice (Cronstein et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Adenosine A₂ receptor‐induced inhibition of leukotriene B₄ synthesis in whole blood ex vivo

Krump

Lemay

Borgeat

1996

British J Pharmacology

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Engagement of adenosine A2 receptors suppresses several leukocyte functions. In the present study, we examined the effect of adenosine on the inhibition of leukotriene B4 (LTB4) synthesis in heparinized human whole blood, pretreated with lipopolysaccharide (LPS) and tumour necrosis factor α (TNF‐α) and stimulated with the chemotactic peptide, N‐formyl‐Met‐Leu‐Phe (FMLP). The FMLP‐induced synthesis of LTB4 in whole blood pretreated with LPS and TNF‐α was dose‐dependently inhibited by adenosine analogues in the following order of potency; 5′(N‐ethyl)carbox‐ amidoadenosine (NECA) ≅ CGS 21680 > 2‐Cl‐adenosine > N6‐cyclopentyladenosine (CPA), indicating the involvement of the adenosine A2 receptor subtype. The IC50 values for NECA, CGS 21680, 2‐Cl‐ adenosine, and CPA were 6nM, 9nM, 180nM, and 990 nM, respectively. Dipyridamole, an agent that blocks the cellular uptake of adenosine by red cells and causes its accumulation in plasma, also inhibited the synthesis of LTB4 in LPS and TNF‐α‐treated whole blood stimulated by FMLP; moreover, this inhibition was reversed upon addition of adenosine deaminase. A highly selective antagonist of the adenosine A2 receptor, 8‐(3‐chlorostyryl)caffeine (CSC), reversed the inhibition of LTB4 synthesis by 2‐Cl‐adenosine and dipyridamole in LPS and TNF‐α‐treated whole blood, stimulated by FMLP. LTB4 synthesis in whole blood originates predominantly from neutrophils and to a lesser extent from monocytes. 2‐Cl‐adenosine also inhibited the synthesis of LTB4 induced by FMLP in these isolated LPS and TNF‐α‐treated cells; however, 2‐Cl‐adenosine was a more potent inhibitor of LTB4 synthesis in neutrophils than monocytes. The present data demonstrate that adenosine, acting through A2 receptors, exerts a potent inhibitory effect on the synthesis of LTB4 and thus contribute to the understanding of its anti‐inflammatory properties.

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Protective Effect of 2-Chloroadenosine on Lung Ischemia Reperfusion Injury

Cited by 13 publications

References 0 publications

Activation of A3 Adenosine Receptor Provides Lung Protection Against Ischemia-Reperfusion Injury Associated with Reduction in Apoptosis

Activation of A3 Adenosine Receptor Provides Lung Protection Against Ischemia-Reperfusion Injury Associated with Reduction in Apoptosis

A_2A adenosine receptors in human peripheral blood cells

Adenosine A₂ receptor‐induced inhibition of leukotriene B₄ synthesis in whole blood ex vivo

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Protective Effect of 2-Chloroadenosine on Lung Ischemia Reperfusion Injury

Cited by 13 publications

References 0 publications

Activation of A3 Adenosine Receptor Provides Lung Protection Against Ischemia-Reperfusion Injury Associated with Reduction in Apoptosis

Activation of A3 Adenosine Receptor Provides Lung Protection Against Ischemia-Reperfusion Injury Associated with Reduction in Apoptosis

A2A adenosine receptors in human peripheral blood cells

Adenosine A2 receptor‐induced inhibition of leukotriene B4 synthesis in whole blood ex vivo

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Product

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A_2A adenosine receptors in human peripheral blood cells

Adenosine A₂ receptor‐induced inhibition of leukotriene B₄ synthesis in whole blood ex vivo