Adenosine and inosine increase cutaneous vasopermeability by activating A3 receptors on mast cells

Tilley, Stephen L.; Wagoner, Victoria A.; Salvatore, Christopher; Jacobson, Marlene A.; Koller, Beverly H.

doi:10.1172/jci8253

Cited by 177 publications

(145 citation statements)

References 42 publications

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“…These findings are also consistent with human studies showing adenosine-induced histamine release from bronchoalveolar lavage mast cells (39). However, these observations do contrast with those of some other studies (2,30,40,41), including one of our own studies in which we showed that while adenosine, acting via the A 3 receptor, could enhance the degranulation of bone marrow mast cells in response to IgE and specific Ag, adenosine alone was ineffective at mediating bone marrow mast cell degranulation (30). However, in this issue Zhong et al (42) demonstrate that adenosine can induce degranulation of mast cells that have been derived in vitro from mouse pulmonary mast cells, a result consistent with the findings in our in vivo studies of mouse airway mast cells in situ.…”

Section: Discussionsupporting

confidence: 90%

“…We previously used mice lacking the A 3 receptor to identify an important role for that receptor in adenosine-induced degranulation of skin mast cells in vivo and in the ensuing adenosine-induced and mast cell-dependent enhancement of cutaneous vascular permeability (30). Here we use wild-type, A 3 -deficient, and mast cell-deficient mice to assess the importance of the A 3 receptor and mast cells in airway responsiveness to adenosine.…”

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confidence: 99%

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Identification of A3 Receptor- and Mast Cell-Dependent and -Independent Components of Adenosine-Mediated Airway Responsiveness in Mice

Tilley

Tsai

Williams

et al. 2003

The Journal of Immunology

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Adenosine-induced bronchoconstriction is a well-recognized feature of atopic asthma. Adenosine acts through four different G protein-coupled receptors to produce a myriad of physiological effects. To examine the contribution of the A3 adenosine receptor to adenosine-induced bronchoconstriction and to assess the contribution of mast cells to this process, we quantified airway responsiveness to aerosolized adenosine in wild-type, A3 receptor-deficient, and mast cell-deficient mice. Compared with the robust airway responses elicited by adenosine in wild-type mice, both A3-deficient and mast cell-deficient mice exhibited a significantly attenuated response compared with their respective wild-type controls. Histological examination of the airways 4 h after adenosine exposure revealed extensive degranulation of airway mast cells as well as infiltration of neutrophils in wild-type mice, whereas these findings were much diminished in A3-deficient mice and were not different from those in PBS-treated controls. These data indicate that the airway responses to aerosolized adenosine in mice occur largely through A3 receptor activation and that mast cells contribute significantly to these responses, but that activation of additional adenosine receptors on a cell type(s) other than mast cells also contributes to adenosine-induced airway responsiveness in mice. Finally, our findings indicate that adenosine exposure can result in A3-dependent airway inflammation, as reflected in neutrophil recruitment, as well as alterations in airway function.

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

Identification of A3 Receptor- and Mast Cell-Dependent and -Independent Components of Adenosine-Mediated Airway Responsiveness in Mice

Tilley

Tsai

Williams

et al. 2003

The Journal of Immunology

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“…8,9 By activating 4 G-protein-coupled adenosine receptors (A 1 , A 2A , A 2B , and A 3 ) on immunocytes, neurons, goblet cells, and ASM, adenosine is believed to contribute to asthma pathogenesis. [8][9][10][11][12][13][14][15][16][17][18][19][20] However, a role for adenosine in the development of AHR has not been previously investigated. In smooth muscle cells, Gerwins and Fredholm 21 demonstrated that adenosine could stimulate Ca 2+ mobilization and enhance the contractile response to activation of G q/11 -coupled receptors.…”

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Adenosine induces airway hyperresponsiveness through activation of A3 receptors on mast cells

Hua

Chason

Fredholm

et al. 2008

Journal of Allergy and Clinical Immunology

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“…Moreover, numerous in vivo and ex vivo studies suggest that A 3 R signaling can influence inflammatory cell types associated with asthma and COPD (16 -22). In rodents, airway mast cells express the A 3 R (22) and engagement of this receptor can promote (22) or enhance (23,24) mediator release from mast cells. In addition, human eosinophils express the A 3 R (25); however, the function of A 3 R signaling on this cell type remains controversial with both pro- (26) and anti- (17) inflammatory activities being reported.…”

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confidence: 99%

A3 Adenosine Receptor Signaling Contributes to Airway Inflammation and Mucus Production in Adenosine Deaminase-Deficient Mice

Young

Molina

Dimina

et al. 2004

The Journal of Immunology

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Adenosine signaling has been implicated in chronic lung diseases such as asthma and chronic obstructive pulmonary disease; however, the specific roles of the various adenosine receptors in processes central to these disorders are not well understood. In this study, we have investigated the role(s) of the A3 adenosine receptor in adenosine-dependent pulmonary inflammation observed in adenosine deaminase (ADA)-deficient mice. The A3 receptor (A3R) was found to be expressed in eosinophils and mucus-producing cells in the airways of ADA-deficient mice. Treatment of ADA-deficient mice with MRS 1523, a selective A3R antagonist, prevented airway eosinophilia and mucus production. Similar findings were seen in the lungs of ADA/A3 double knockout mice. Although eosinophils were decreased in the airways of ADA-deficient mice following antagonism or removal of the A3R, elevations in circulating and lung interstitial eosinophils persisted, suggesting signaling through the A3R is needed for the migration of eosinophils into the airways. These findings identify an important role for the A3R in regulating lung eosinophilia and mucus production in an environment of elevated adenosine.

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Adenosine and inosine increase cutaneous vasopermeability by activating A3 receptors on mast cells

Cited by 177 publications

References 42 publications

Identification of A3 Receptor- and Mast Cell-Dependent and -Independent Components of Adenosine-Mediated Airway Responsiveness in Mice

Identification of A3 Receptor- and Mast Cell-Dependent and -Independent Components of Adenosine-Mediated Airway Responsiveness in Mice

Adenosine induces airway hyperresponsiveness through activation of A3 receptors on mast cells

A3 Adenosine Receptor Signaling Contributes to Airway Inflammation and Mucus Production in Adenosine Deaminase-Deficient Mice

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