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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Adenosine-Mediated Mast Cell Degranulation in Adenosine Deaminase-Deficient Mice

Hongyan Zhong, Janci L. Chunn, Jonathan B. Volmer, John R. Fozard and Michael R. Blackburn
Journal of Pharmacology and Experimental Therapeutics August 2001, 298 (2) 433-440;
Hongyan Zhong
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Janci L. Chunn
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Jonathan B. Volmer
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John R. Fozard
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Michael R. Blackburn
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Abstract

Adenosine is a signaling nucleoside that has been suggested to play a role in asthma in part through its ability to influence mediator release from mast cells. Adenosine levels are elevated in the lungs of asthmatics, further implicating this molecule in the regulation of lung inflammation and suggesting that animal models exhibiting endogenous increases in adenosine will be useful for the analysis of adenosine function. Adenosine deaminase (ADA) is a purine catabolic enzyme responsible for regulating the levels of adenosine in tissues and cells. ADA-deficient mice develop lung inflammation and damage reminiscent of that seen in asthma in association with elevated adenosine levels. In the current study, we investigated the status of mast cells in ADA-deficient lungs. ADA-deficient mice exhibited extensive lung mast cell degranulation concurrent with elevated adenosine levels. ADA enzyme therapy prevented the accumulation of lung adenosine as well as mast cell degranulation, suggesting that this process was dependent on elevated lung adenosine levels. Consistent with this, treatment of ADA-deficient mice with broad spectrum adenosine receptor antagonists attenuated degranulation by 30 to 40%, supporting the involvement of adenosine receptor signaling. Moreover, these studies demonstrate the ability of endogenously generated adenosine to influence lung mast cell degranulation in a receptor-mediated manner and establish ADA-deficient mice as a model system to investigate the specific adenosine receptor responses involved in the degranulation of lung mast cells.

Footnotes

  • This work was supported by Grants AI43572 and HL61888 from the National Institutes of Health (to M.R.B.).

  • Abbreviations:
    ADA
    adenosine deaminase
    PEG-ADA
    polyethylene glycol-modified-ADA
    PBS
    phosphate-buffered saline
    • Received February 6, 2001.
    • Accepted May 1, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 298 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 298, Issue 2
1 Aug 2001
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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Adenosine-Mediated Mast Cell Degranulation in Adenosine Deaminase-Deficient Mice

Hongyan Zhong, Janci L. Chunn, Jonathan B. Volmer, John R. Fozard and Michael R. Blackburn
Journal of Pharmacology and Experimental Therapeutics August 1, 2001, 298 (2) 433-440;

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Research ArticleINFLAMMATION AND IMMUNOPHARMACOLOGY

Adenosine-Mediated Mast Cell Degranulation in Adenosine Deaminase-Deficient Mice

Hongyan Zhong, Janci L. Chunn, Jonathan B. Volmer, John R. Fozard and Michael R. Blackburn
Journal of Pharmacology and Experimental Therapeutics August 1, 2001, 298 (2) 433-440;
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