Adenosine 5′-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation

Bours, Martijn Jan Leo; Swennen, Els L.R.; Virgilio, Francesco Di; Cronstein, Bruce N.; Dagnelie, Pieter C.

doi:10.1016/j.pharmthera.2005.04.013

Cited by 898 publications

(962 citation statements)

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“…Growing evidence shows that extracellular nucleotides play key roles in inflammatory neutrophil migration. ATP enhances neutrophil adhesion and extravasation (Bours et al, 2006;Dawicki et al, 1995), and also chemotaxis via P2Y 2 receptor (Chen et al, 2006;Junger, 2008;Kukulski et al, 2009). In keeping with these data, mice deficient in ATP-dependent P2Y 2 receptor exhibit an impaired neutrophil recruitment in sepsis (Inoue et al, 2008).…”

Section: Introductionsupporting

confidence: 54%

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The P2 receptor antagonist PPADS abrogates LPS-induced neutrophil migration in the murine air pouch via inhibition of MIP-2 and KC production

Kukulski

Yebdri

Bahrami

et al. 2010

Molecular Immunology

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In this work, we show that P2 nucleotide receptors control lipopolysaccharide (LPS)-induced neutrophil migration in the mouse air pouch model. Neutrophil infiltration in LPS-treated air pouches was reduced by the intravenous (iv) administration of the non-selective P2 receptor antagonist PPADS but not by suramin and RB-2. In addition, the iv administration of a P2 receptor ligand, UTP, enhanced LPS-induced neutrophil migration. In contrast, the iv injection of UDP had no effect on neutrophil migration. These data suggest that LPS-induced neutrophil migration in the air pouch could involve P2Y 4 receptor which is antagonized by PPADS, activated by UTP, but not UDP, and insensitive to suramin. The inhibition of neutrophil migration by PPADS correlated with a diminished secretion of chemokines macrophage inflammatory protein-2 (MIP-2) and keratinocyte-derived chemokine (KC) in the air pouch exudates. As determined in vitro, PPADS did not affect MIP-2 and KC release from air pouch resident cells nor from accumulated neutrophils. MIP-2 and KC production in the LPS-treated air pouches correlated with an early neutrophil migration (1 h after LPS injection), and both of these effects were significantly reduced in mice administered with PPADS. Altogether, these data suggest that P2Y 4 receptor expressed in circulating leukocytes and/or endothelium controls LPS-induced acute neutrophil recruitment in mouse air pouch.

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Section: Introductionsupporting

confidence: 54%

“…All P2X and P2Y 11 receptors are activated by ATP, P2Y 2 by ATP and UTP, P2Y 1 , P2Y 12 and P2Y 13 by ADP, P2Y 4 by UTP, P2Y 6 by UDP and P2Y 14 by UDPglucose (Bours et al, 2006). Growing evidence shows that extracellular nucleotides play key roles in inflammatory neutrophil migration.…”

Section: Introductionmentioning

confidence: 99%

The P2 receptor antagonist PPADS abrogates LPS-induced neutrophil migration in the murine air pouch via inhibition of MIP-2 and KC production

Kukulski

Yebdri

Bahrami

et al. 2010

Molecular Immunology

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“…Extracellular ATP acts as a ''danger signal'' when it is released from cells during tissue damage and inflammation; it acts on metabotropic (G-protein coupled) P2Y and ionotropic (cation channel) P2X purinergic receptors to affect several inflammatory and immune responses [1,2]. There are seven members of the P2X receptor family (P2X 1-7 R) that show widespread distribution in both neuronal and non-neuronal tissues [3].…”

Section: Introductionmentioning

confidence: 99%

“…Two of these seven members, P2X 4 R and P2X 7 R, have generated increasing interest as potential anti-inflammatory drug targets [2,4,5]. The case for P2X 7 R is now well established: Stimulation of P2X 7 R in activated monocytes, macrophages and microglia leads to rapid release of pro-inflammatory IL-1b and IL-18 cytokines, to phospholipase D activation and, if stimulation is sustained, to apopotosis [1,[3][4][5]. Classical activation of macrophages, generally induced by IFN-g and/or LPS, up-regulates P2X 7 R mRNA and protein levels and functional expression [6,7] and this correlates well with a role for P2X 7 R in bacterial killing [8,9].…”

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confidence: 99%

Dynamic regulation of the P2X₄ receptor in alveolar macrophages by phagocytosis and classical activation

Stokes

Surprenant

2009

Eur J Immunol

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ATP-gated P2X 4 receptors (P2X 4 R) in macrophages and microglia have been implicated in neuropathic and inflammatory pain by currently unidentified mechanisms. P2X 4 R are found predominantly in intracellular lysosomal compartments but can be rapidly trafficked to the surface membrane by procedures that induce endolysosomal secretion. We studied total and surface membrane P2X 4 R protein expression by Western blot and biotinylation assays and functional expression by whole-cell patch clamp assays in human and rat alveolar macrophages in response to phagocytosis of zymosan and opsonized zymosan bioparticles and to classical and alternative macrophage activation. Unstimulated macrophages showed high total protein expression but very low functional expression. Phagocytosis rapidly (within 4 h) increased functional P2X 4 R expression by 2-to 7-fold as did chloroquine, an agent known to induce lysosomal secretion. In contrast, classical activation of macrophage for 48 h with IFN-c and TNF-a or IFN-c and LPS reduced surface and functional P2X 4 R expression by 3-fold without altering total P2X 4 R protein levels. Alternative activation with IL-4 or IL-13 did not alter total, surface or functional expression of P2X 4 R. This is the first study of the regulation of P2X 4 R in macrophages by physiological stimuli and presents a picture whereby P2X 4 R become functional in response to initial phagocytic stimuli but return to a non-functional state during sustained activation by classical macrophage activation.Key words: Inflammation . Ion channels . Patch-clamp . Purine receptors Introduction Extracellular ATP acts as a ''danger signal'' when it is released from cells during tissue damage and inflammation; it acts on metabotropic (G-protein coupled) P2Y and ionotropic (cation channel) P2X purinergic receptors to affect several inflammatory and immune responses [1,2]. There are seven members of the P2X receptor family (P2X 1-7 R) that show widespread distribution in both neuronal and non-neuronal tissues [3]. Two of these seven members, P2X 4 R and P2X 7 R, have generated increasing interest as potential anti-inflammatory drug targets [2,4,5]. The case for P2X 7 R is now well established: Stimulation of P2X 7 R in activated monocytes, macrophages and microglia leads to rapid release of pro-inflammatory IL-1b and IL-18 cytokines, to phospholipase D activation and, if stimulation is sustained, to apopotosis [1,[3][4][5]. Classical activation of macrophages, generally induced by IFN-g and/or LPS, up-regulates P2X 7 R mRNA and protein levels and functional expression [6,7] and this correlates well with a role for P2X 7 R in bacterial killing [8,9]. Recently, highly selective and potent P2X 7 R antagonists have been identified [10] with one of these showing initial positive results in Phase II clinical trials for rheumatoid arthritis [11]. The case for P2X 4 R remains tentative, largely due to the absence of selective P2X 4 R antagonists and the complicating presence of P2X 7 R, which is generally co-expressed with P2X 4 R in ...

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“…L'adénosine est relarguée par les cellules dans le milieu extracellulaire. Sa concentration dans les vaisseaux sanguins est faible car elle est rapidement internalisée par les globules rouges [18], ce qui n'est pas le cas dans les tissus interstitiels. Au site inflammatoire, l'accumulation d'adénosine peut être importante en raison de la libération d'ATP (hydrolysé en adénosine par les 5'-nucléotidases) par les cellules endommagées ou ischémi-ques et de l'augmentation du nombre de neutrophiles.…”

Section: Polynucléaires Neutrophiles Et Résolution Du Processus Inflaunclassified

Le neutrophile : ennemi ou ami ?

Dumas

Pouliot

2009

Med Sci (Paris)

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Les polynucléaires neutrophiles (PN) sont des agents de premier plan de l'immunité innée, particulièrement lors de la réaction inflammatoire ; ils sont souvent les premiers leucocytes à migrer en grand nombre vers le site enflammé. La réaction inflammatoire est le plus souvent protectrice car elle participe à la défense naturelle de l'organisme et à la réparation des tissus lésés. Malheureusement, si elle est inadaptée ou mal régulée, l'inflammation peut devenir nocive. Ainsi le neutrophile est mis en cause dans la pathogenèse de nombreuses maladies inflammatoires chroniques, comme la polyarthrite rhumatoïde et, en particulier, pour les altérations qu'il cause aux tissus et la dégradation des articulations qui en résulte. Les traitements anti-inflammatoires classiques parviennent à atténuer les symptômes de l'inflammation comme la fièvre, la douleur et l'enflure mais aucun ne permet la guérison. Plusieurs indices suggèrent qu'ils n'empêchent pas l'action destructrice des neutrophiles et pourraient même aggraver la progression des dommages. De meilleures stratégies pourraient consister à augmenter l'efficacité des systèmes de régulation endogènes à l'origine de la sécrétion de molécules anti-inflammatoires. Après un bref rappel des fonctions pro-inflammatoires du neutrophile, cet article mettra l'accent sur les capacités qu'ont ces cellules d'arrêter le processus d'inflammation et l'état de la recherche sur les mécanismes en cause.Le polynuléaire neutrophile, une première ligne de défense pour l'organisme Fonctions de base des PN : élimination des agents infectieux L'action anti-infectieuse du neutrophile repose sur ses capacités de migration transendothéliale, de phagocytose, « d'explosion oxydative » et de dégranulation [1]. De manière physiologique, les PN transitent dans la circulation sanguine en « roulant » sur les cellules endothéliales de la paroi vasculaire (processus de rolling). En réponse à la détection de produits bactériens (peptides formylés, lipopolysaccharides) ou sous l'influence de molécules attractives [leucotriène (LT)B 4 , la chimiokine CXCL8 ou IL(interleukine)-8, fragments du complément, etc.], le PN exprime à sa surface des molécules d'adhé-rence qui vont lui permettre de traverser la paroi endothéliale et de migrer vers le site enflammé. Il reconnaît spécifiquement des motifs présents à la surface des micro-organismes (bactéries, virus), ce qui déclenche leur phagocytose. La dégradation des pathogènes ainsi ingérés s'effectue par deux mécanismes concomitants : la production de formes réactives de l'oxygène (ROS : reactive oxygen species) par la NADPH oxydase et la libé-ration, par les granules des PN, de protéines enzymatiques (myéloperoxydase, élastases, lysosyme, gélatinase)

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Adenosine 5′-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation

Cited by 898 publications

References 675 publications

The P2 receptor antagonist PPADS abrogates LPS-induced neutrophil migration in the murine air pouch via inhibition of MIP-2 and KC production

The P2 receptor antagonist PPADS abrogates LPS-induced neutrophil migration in the murine air pouch via inhibition of MIP-2 and KC production

Dynamic regulation of the P2X₄ receptor in alveolar macrophages by phagocytosis and classical activation

Le neutrophile : ennemi ou ami ?

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Adenosine 5′-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation

Cited by 898 publications

References 675 publications

The P2 receptor antagonist PPADS abrogates LPS-induced neutrophil migration in the murine air pouch via inhibition of MIP-2 and KC production

The P2 receptor antagonist PPADS abrogates LPS-induced neutrophil migration in the murine air pouch via inhibition of MIP-2 and KC production

Dynamic regulation of the P2X4 receptor in alveolar macrophages by phagocytosis and classical activation

Le neutrophile : ennemi ou ami ?

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Dynamic regulation of the P2X₄ receptor in alveolar macrophages by phagocytosis and classical activation