Extracellular ATP triggers and maintains asthmatic airway inflammation by activating dendritic cells

Idzko, Marco; Hammad, Hamida; Nimwegen, Menno van; Kool, Mirjam; Willart, Monique; Muskens, Femke; Hoogsteden, Henk C.; Luttmann, Werner; Ferrari, Davide; Virgilio, Francesco Di; Virchow, J. Christian; Lambrecht, Bart N.

doi:10.1038/nm1617

Cited by 553 publications

(598 citation statements)

References 49 publications

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“…oATP was successfully applied to limit T cellmediated inflammation in mouse models of type 1 diabetes and inflammatory bowel disease [29,118]. oATP, suramine, and pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid significantly reduced allergic airway inflammatory response in the OVA-mediated model of asthma [91]. Thus, purinergic receptor blockade might represent a promising therapeutic strategy for the treatment of a number of inflammatory diseases including allergy in which mast cells are recognized to play an effector role.…”

Section: Discussionmentioning

confidence: 99%

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P2 receptor-mediated signaling in mast cell biology

Bulanova

Bulfone–Paus∥

2009

Purinergic Signalling

100

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Mast cells are widely recognized as effector cells of allergic inflammatory reactions. They contribute to the pathogenesis of different chronic inflammatory diseases, wound healing, fibrosis, thrombosis/fibrinolysis, and antitumor immune responses. In this paper, we summarized the role of P2X and P2Y receptors in mast cell activation and effector functions. Mast cells are an abundant source of ATP which is stored in their granules and secreted upon activation. We discuss the contribution of mast cells to the extracellular ATP release and to the maintenance of extracellular nucleotides pool. Recent publications highlight the importance of purinergic signaling for the pathogenesis of chronic airway inflammation. Therefore, the role of ATP and P2 receptors in allergic inflammation with focus on mast cells was analyzed. Finally, ATP functions as mast cell autocrine/paracrine factor and as messenger in intercellular communication between mast cells, nerves, and glia in the central nervous system.

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Section: Discussionmentioning

confidence: 99%

“…2). In fact, recent observation shows that ATP levels are significantly elevated in the airways of asthmatic patients after allergen challenge and in mice in a model of ovalbumin (OVA)-induced asthma [91]. Aerosolized ATP triggers bronchoconstriction in healthy and asthmatic individuals [92].…”

Section: Purinergic Signaling In Allergic Airway Inflammation: Focus mentioning

confidence: 99%

P2 receptor-mediated signaling in mast cell biology

Bulanova

Bulfone–Paus∥

2009

Purinergic Signalling

100

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“…ATP is reported to be important for the genesis and maintenance of this disease. For instance, ATP triggers and maintains asthmatic inflammation by activating DCs and enhancing its Th2-priming capacity [134,135]. Another study demonstrated that this allergic inflammation in humans and mice is associated with the functional up-regulation of P2X7 receptor expression on immune cells (macrophages and eosinophils) and that P2X7 receptor signaling (e.g., via modulating of DC function) is involved in ATP-mediated pro-asthmatic effects [136].…”

Section: Pulmonary Epithelium Injurymentioning

confidence: 99%

Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration

Glaser

Cappellari

Pillat

et al. 2011

Purinergic Signalling

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Replacement of lost or dysfunctional tissues by stem cells has recently raised many investigations on therapeutic applications. Purinergic signaling has been shown to regulate proliferation, differentiation, cell death, and successful engraftment of stem cells originated from diverse origins. Adenosine triphosphate release occurs in a controlled way by exocytosis, transporters, and lysosomes or in large amounts from damaged cells, which is then subsequently degraded into adenosine. Paracrine and autocrine mechanisms induced by immune responses present critical factors for the success of stem cell therapy. While P1 receptors generally exert beneficial effects including anti-inflammatory activity, P2 receptor-mediated actions depend on the subtype of stimulated receptors and localization of tissue repair. Pro-inflammatory actions and excitatory tissue damages mainly result from P2X7 receptor activation, while other purinergic receptor subtypes participate in proliferation and differentiation, thereby providing adequate niches for stem cell engraftment and novel mechanisms for cell therapy and endogenous tissue repair. Therapeutic applications based on regulation of purinergic signaling are foreseen for kidney and heart muscle regeneration, Clara-like cell replacement for pulmonary and bronchial epithelial cells as well as for induction of neurogenesis in case of neurodegenerative diseases.

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“…Extracellular Ado appears to be an important immunosuppressive and tissue-healing factor. Like ATP, Ado can also be considered a danger molecule because its extracellular levels rise markedly in response to tissue damage [13,66,122].…”

Section: Immunomodulation and Cell-cell Interactionsmentioning

confidence: 99%

NTPDase and 5'‐nucleotidase activities in physiological and disease conditions: New perspectives for human health

et al. 2007

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Abstract. Extracellular nucleotides and nucleosides act as signaling molecules involved in a wide spectrum of biological effects. Their levels are controlled by a complex cell surface-located group of enzymes called ectonucleotidases. There are four major families of ectonucleotidases, nucleoside triphosphate diphosphohydrolases (NTPDases/CD39), ectonucleotide pyrophosphatase/phosphodiesterases (E-NPPs), alkaline phosphatases and ecto-5'-nucleotidase. In the last few years, substantial progress has been made toward the molecular identification of members of the ectonucleotidase families and their enzyme structures and functions. In this review, there is an emphasis on the involvement of NTPDase and 5'-nucleotidase activities in disease processes in several tissues and cell types. Brief background information is given about the general characteristics of these enzymes, followed by a discussion of their roles in thromboregulatory events in diabetes, hypertension, hypercholesterolemia and cancer, as well as in pathological conditions where platelets are less responsive, such as in chronic renal failure. In addition, immunomodulation and cell-cell interactions involving these enzymes are considered, as well as ATP and ADP hydrolysis under different clinical conditions related with alterations in the immune system, such as acute lymphoblastic leukemia (ALL), Bchronic lymphocytic leukemia (B-CLL) and infections associated with human immunodeficiency virus (HIV). Finally, changes in ATP, ADP and AMP hydrolysis induced by inborn errors of metabolism, seizures and epilepsy are discussed in order to highlight the importance of these enzymes in the control of neuronal activity in pathological conditions. Despite advances made toward understanding the molecular structure of ectonucleotidases, much more investigation will be necessary to entirely grasp their role in physiological and pathological conditions.

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Extracellular ATP triggers and maintains asthmatic airway inflammation by activating dendritic cells

Cited by 553 publications

References 49 publications

P2 receptor-mediated signaling in mast cell biology

P2 receptor-mediated signaling in mast cell biology

Perspectives of purinergic signaling in stem cell differentiation and tissue regeneration

NTPDase and 5'‐nucleotidase activities in physiological and disease conditions: New perspectives for human health

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