Role of Extracellular ATP and P1 and P2 Classes of Purinergic Receptors in T‐cell Development and Cytotoxic T Lymphocyte Effector Functions

Apasov, Sergey; Koshiba, Masanori; Redegeld, Frank A.; Sitkovsky, Michail V.

doi:10.1111/j.1600-065x.1995.tb00680.x

Cited by 89 publications

(66 citation statements)

References 38 publications

(14 reference statements)

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“…The nucleoside adenosine is the best characterized of these purines, as both extracellular and intracellular adenosine have been shown to affect almost all aspects of an immune response (1)(2)(3). Adenosine and its analogues can alter the course of a variety of immunemediated/inflammatory diseases such as endotoxin shock (4,5), rheumatoid arthritis (6,7), pleural inflammation (8), nephritis (9), or uveitis (10).…”

mentioning

confidence: 99%

“…In inflammatory diseases and ischemic processes, large amounts of cytokines are produced, causing edema, cellular metabolic stress, and finally tissue necrosis. The proinflammatory cytokines TNF-␣, IL-1, IL-12, macrophage-inflammatory protein (MIP 3 )-1␣, MIP-2, and IFN-␥ are primarily involved in promoting inflammatory processes, and they also play an important role in ischemia-reperfusion injury (21)(22)(23)(24)(25)(26). On the other hand, IL-10 is an anti-inflammatory cytokine that decreases inflammation and also has protective effects in ischemic processes (26,27).…”

mentioning

confidence: 99%

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Inosine Inhibits Inflammatory Cytokine Production by a Posttranscriptional Mechanism and Protects Against Endotoxin-Induced Shock

Haskó

Kuhel

Németh

et al. 2000

The Journal of Immunology

294

230

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Extracellular purines, including adenosine and ATP, are potent endogenous immunomodulatory molecules. Inosine, a degradation product of these purines, can reach high concentrations in the extracellular space under conditions associated with cellular metabolic stress such as inflammation or ischemia. In the present study, we investigated whether extracellular inosine can affect inflammatory/immune processes. In immunostimulated macrophages and spleen cells, inosine potently inhibited the production of the proinflammatory cytokines TNF-α, IL-1, IL-12, macrophage-inflammatory protein-1α, and IFN-γ, but failed to alter the production of the anti-inflammatory cytokine IL-10. The effect of inosine did not require cellular uptake by nucleoside transporters and was partially reversed by blockade of adenosine A1 and A2 receptors. Inosine inhibited cytokine production by a posttranscriptional mechanism. The activity of inosine was independent of activation of the p38 and p42/p44 mitogen-activated protein kinases, the phosphorylation of the c-Jun terminal kinase, the degradation of inhibitory factor κB, and elevation of intracellular cAMP. Inosine suppressed proinflammatory cytokine production and mortality in a mouse endotoxemic model. Taken together, inosine has multiple anti-inflammatory effects. These findings, coupled with the fact that inosine has very low toxicity, suggest that this agent may be useful in the treatment of inflammatory/ischemic diseases.

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confidence: 99%

mentioning

confidence: 99%

Inosine Inhibits Inflammatory Cytokine Production by a Posttranscriptional Mechanism and Protects Against Endotoxin-Induced Shock

Haskó

Kuhel

Németh

et al. 2000

The Journal of Immunology

294

230

View full text Add to dashboard Cite

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“…P2Y 4 is present in the intestine, lung and placenta [6]. UTP is a potent agonist at P2Y 4 . Expression of P2Y 6 has been found in many human tissues, including spleen, thymus, placenta, intestine, lung and brain [6,11,12].…”

Section: P2 Receptorsmentioning

confidence: 99%

“…Two P2 receptor subfamilies have been described so far and named P2Y and P2X. Members of the two groups differ in protein structure, pharmacology and function [3][4][5]. P2Y receptors are seven membrane-spanning, G-proteincoupled receptors whose activation triggers generation of inositol 1,4,5-trisphosphate and release of Ca 2+ from the intracellular stores [6].…”

Section: P2 Receptorsmentioning

confidence: 99%

Shaping immune responses through the activation of dendritic cells’ P2 receptors

Ferrari

Gorini

Callegari

et al. 2006

Purinergic Signalling

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Dendritic cells (DCs) activate and shape the adaptive immune response by capturing antigens, migrating to peripheral lymphoid organs where naïve T cells reside, expressing high levels of MHC and costimulatory molecules and by secreting cytokines and chemokines. DCs are endowed with a high degree of functional plasticity and their functions are tightly regulated. Besides initiating adaptive immune responses, DCs play a key role in maintaining peripheral tolerance toward self-antigens. On the basis of the information gathered from the tissue where they reside DCs adjust their functional activity to ensure that protective immunity is favored while unwanted or exaggerated immune responses are prevented. A wide variety of signals from neighbouring cells affecting DCs functional activity have been described. Here we will discuss the complex role of extracellular nucleotides in the regulation of DCs function and the role of P2 receptors as possible tools to manipulate immune responses.

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“…15) Of the P2 receptors, P2X 1 and P2X 7 are reportedly sensitive to extracellular ATP. 16,17) ATP-mediated death in macrophages is caused by activation of P2X 7 , which leads to apoptosis. 18) Additionally, it has been found that P2X 7 receptor mRNA is expressed in bone marrow and in tissues containing abundant macrophages or monocytes.…”

mentioning

confidence: 99%

Extracellular ATP Is Involved in the Induction of Apoptosis in Murine Hematopoietic Cells

Yoon

Lee

et al. 2007

Biological & Pharmaceutical Bulletin

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Role of Extracellular ATP and P1 and P2 Classes of Purinergic Receptors in T‐cell Development and Cytotoxic T Lymphocyte Effector Functions

Cited by 89 publications

References 38 publications

Inosine Inhibits Inflammatory Cytokine Production by a Posttranscriptional Mechanism and Protects Against Endotoxin-Induced Shock

Inosine Inhibits Inflammatory Cytokine Production by a Posttranscriptional Mechanism and Protects Against Endotoxin-Induced Shock

Shaping immune responses through the activation of dendritic cells’ P2 receptors

Extracellular ATP Is Involved in the Induction of Apoptosis in Murine Hematopoietic Cells

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