Species differences in adenosine receptor‐mediated bronchoconstrictor responses

Fozard, John R.; Hannon, Jason P.

doi:10.1046/j.1365-2222.2000.00894.x

Cited by 48 publications

(44 citation statements)

References 55 publications

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“…Exogenous adenosine has been shown to induce bronchoconstriction in asthmatics (17) and various animal models (32). To determine whether the endogenous accumulation of adenosine in the lungs was associated with alterations in airway physiology, airway hyperresponsiveness was measured in 6-wk-old partially ADAdeficient mice.…”

Section: Partially Ada-deficient Mice Exhibit Increased Basal Penh Vamentioning

confidence: 99%

Adenosine-Dependent Airway Inflammation and Hyperresponsiveness in Partially Adenosine Deaminase-Deficient Mice

Chunn¹,

Young²,

Banerjee³

et al. 2001

The Journal of Immunology

135

120

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Adenosine is a signaling nucleoside that is elevated in the lungs of asthmatics. We have engineered a mouse model that has elevated levels of adenosine as a result of the partial expression of the enzyme that metabolizes adenosine, adenosine deaminase (ADA). Mice with lowered levels of ADA enzymatic activity were generated by the ectopic expression of an ADA minigene in the gastrointestinal tract of otherwise ADA-deficient mice. These mice developed progressive lung inflammation and damage and died at 4–5 mo of age from respiratory distress. Associated with this phenotype was a progressive increase in lung adenosine levels. Examination of airway physiology at 6 wk of age revealed alterations in airway hyperresponsiveness. This was reversed following the lowering of adenosine levels using ADA enzyme therapy and also through the use of the adenosine receptor antagonist theophylline, implicating both the nucleoside and its receptors in airway physiological alterations. All four adenosine receptors were expressed in the lungs of both control and partially ADA-deficient mice. However, transcript levels for the A1, A2B, and A3 adenosine receptors were significantly elevated in partially ADA-deficient lungs. There was a significant increase in alveolar macrophages, and monocyte chemoattractant protein-3 was found to be elevated in the bronchial epithelium of these mice, which may have important implications in the regulation of pulmonary inflammation and airway hyperresponsiveness. Collectively, these findings suggest that elevations in adenosine can directly impact lung inflammation and physiology.

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Section: Partially Ada-deficient Mice Exhibit Increased Basal Penh Vamentioning

confidence: 99%

Adenosine-Dependent Airway Inflammation and Hyperresponsiveness in Partially Adenosine Deaminase-Deficient Mice

Chunn¹,

Young²,

Banerjee³

et al. 2001

The Journal of Immunology

135

120

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“…However, the relative contributions of the proposed mast cell-dependent and mast cell-independent components of adenosine-induced bronchoconstriction differ among species (16). For example, rabbits are thought to have a large mast cell-independent component, reflecting direct actions of adenosine on airway smooth muscle (ASM) (17), whereas findings in humans (18,19) and rats (20,21) indicate that these species may have a large mast cell-dependent component to adenosine responsiveness.…”

mentioning

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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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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“…Different adenosine receptors are coupled to different G proteins and preferentially expressed by specific cell types. In asthmatic subjects, adenosine-mediated signaling in mast cells is thought to be central to inducing bronchoconstriction, an effect that has been utilized by many authors to diagnose airway hyperreactivity (2,11). One of the targets of theophylline, a therapeutic drug for the treatment of asthma and COPD are the adenosine receptors.…”

Section: Adenosine Signaling and Tissue Injurymentioning

confidence: 99%

“…One of the targets of theophylline, a therapeutic drug for the treatment of asthma and COPD are the adenosine receptors. Adenosine also has significant effects in organs other than the lungs (10)(11)(12). In the immune system, high, uncontrolled levels of adenosine metabolites (as seen in ADA deficiency) are toxic to lymphocytes (12) and it is via this mechanism that ADA deficiency causes SCID in both humans and mice.…”

Section: Adenosine Signaling and Tissue Injurymentioning

confidence: 99%

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IL-13 and adenosine: partners in a molecular dance?

Grünig¹

2003

J. Clin. Invest.

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Inflammation and airway remodeling are two responses readily apparent in asthma and other inflammatory disorders of the airway and lungs. Both adenosine and IL-13 play critical roles in contributing pathways. A new study (see the related article beginning on page 332) reveals a previously unrecognized interaction between adenosine and IL-13 that indicates a mutual stimulation that may contribute to the nature and severity of airway inflammation and fibrosis.

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Species differences in adenosine receptor‐mediated bronchoconstrictor responses

Cited by 48 publications

References 55 publications

Adenosine-Dependent Airway Inflammation and Hyperresponsiveness in Partially Adenosine Deaminase-Deficient Mice

Adenosine-Dependent Airway Inflammation and Hyperresponsiveness in Partially Adenosine Deaminase-Deficient Mice

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

IL-13 and adenosine: partners in a molecular dance?

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