腺苷
腺苷脱氨酶
腺苷受体
腺苷A3受体
嘌呤能信号
内分泌学
内科学
炎症
腺苷A1受体
受体
生物
免疫学
医学
兴奋剂
作者
Janci L. Chunn,Hays W. J. Young,Suman K. Banerjee,Giuseppe N. Colasurdo,Michael R. Blackburn
出处
期刊:Journal of Immunology
[American Association of Immunologists]
日期:2001-10-15
卷期号:167 (8): 4676-4685
被引量:145
标识
DOI:10.4049/jimmunol.167.8.4676
摘要
Abstract 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.
科研通智能强力驱动
Strongly Powered by AbleSci AI