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This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/L753    most recent 00187.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Mohsenin, A. Articles by Blackburn, M. R. Search for Related Content PubMed PubMed Citation Articles by Mohsenin, A. Articles by Blackburn, M. R.

Genetic removal of the A_2A adenosine receptor enhances pulmonary inflammation, mucin production, and angiogenesis in adenosine deaminase-deficient mice

¹Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, and ²The Graduate School of Biomedical Sciences, University of Texas, Houston, Texas; and ³Department of Neurology, Boston University School of Medicine, Boston, Massachusetts

Submitted 11 May 2007 ; accepted in final form 26 June 2007

Adenosine is generated at sites of tissue injury where it serves to regulate inflammation and damage. Adenosine signaling has been implicated in the regulation of pulmonary inflammation and damage in diseases such as asthma and chronic obstructive pulmonary disease; however, the contribution of specific adenosine receptors to key immunoregulatory processes in these diseases is still unclear. Mice deficient in the purine catabolic enzyme adenosine deaminase (ADA) develop pulmonary inflammation and mucous metaplasia in association with adenosine elevations making them a useful model for assessing the contribution of specific adenosine receptors to adenosine-mediated pulmonary disease. Studies suggest that the A_2A adenosine receptor (A_2AR) functions to limit inflammation and promote tissue protection; however, the contribution of A_2AR signaling has not been examined in the ADA-deficient model of adenosine-mediated lung inflammation. The purpose of the current study was to examine the contribution of A_2AR signaling to the pulmonary phenotype seen in ADA-deficient mice. This was accomplished by generating ADA/A_2AR double knockout mice. Genetic removal of the A_2AR from ADA-deficient mice resulted in enhanced inflammation comprised largely of macrophages and neutrophils, mucin production in the bronchial airways, and angiogenesis, relative to that seen in the lungs of ADA-deficient mice with the A_2AR. In addition, levels of the chemokines monocyte chemoattractant protein-1 and CXCL1 were elevated, whereas levels of cytokines such as TNF- and IL-6 were not. There were no compensatory changes in the other adenosine receptors in the lungs of ADA/A_2AR double knockout mice. These findings suggest that the A_2AR plays a protective role in the ADA-deficient model of pulmonary inflammation.

inflammation; chemokines; asthma; adenosine receptors

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