| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Biochemistry and Molecular Biology and
Pediatrics, University of Texas Health Science Center, Houston Medical School, Houston, TX 77030
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.
This article has been cited by other articles:
|
|
 |
|
  J.-N. Yang, O. Bjorklund, K. Lindstrom-Tornqvist, E. Lindgren, T. M. Eriksson, J. Kahlstrom, J.-F. Chen, M. A. Schwarzschild, I. Tobler, and B. B. Fredholm Mice heterozygous for both A1 and A2A adenosine receptor genes show similarities to mice given long-term caffeine J Appl Physiol, February 1, 2009; 106(2): 631 - 639. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Morschl, J. G. Molina, J. B. Volmer, A. Mohsenin, R. S. Pero, J.-S. Hong, F. Kheradmand, J. J. Lee, and M. R. Blackburn A3 Adenosine Receptor Signaling Influences Pulmonary Inflammation and Fibrosis Am. J. Respir. Cell Mol. Biol., December 1, 2008; 39(6): 697 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Esther Jr, N. E. Alexis, M. L. Clas, E. R. Lazarowski, S. H. Donaldson, C. M. Pedrosa Ribeiro, C. G. Moore, S. D. Davis, and R. C. Boucher Extracellular purines are biomarkers of neutrophilic airway inflammation Eur. Respir. J., May 1, 2008; 31(5): 949 - 956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Ponnoth, A. Nadeem, and S. J. Mustafa Adenosine-mediated alteration of vascular reactivity and inflammation in a murine model of asthma Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2158 - H2165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Sun, F. Wu, F. Sun, and P. Huang Adenosine Promotes IL-6 Release in Airway Epithelia J. Immunol., March 15, 2008; 180(6): 4173 - 4181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Brown, G. W. Clarke, C. L. Ledbetter, M. J. Hurle, J. C. Denyer, D. E. Simcock, J. E. Coote, T. J. Savage, R. D. Murdoch, C. P. Page, et al. Elevated expression of adenosine A1 receptor in bronchial biopsy specimens from asthmatic subjects Eur. Respir. J., February 1, 2008; 31(2): 311 - 319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mohsenin, T. Mi, Y. Xia, R. E. Kellems, J.-F. Chen, and M. R. Blackburn Genetic removal of the A2A adenosine receptor enhances pulmonary inflammation, mucin production, and angiogenesis in adenosine deaminase-deficient mice Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L753 - L761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mohsenin, M. D. Burdick, J. G. Molina, M. P. Keane, and M. R. Blackburn Enhanced CXCL1 production and angiogenesis in adenosine-mediated lung disease FASEB J, April 1, 2007; 21(4): 1026 - 1036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Factor, G. M. Mutlu, L. Chen, J. Mohameed, A. T. Akhmedov, F. J. Meng, T. Jilling, E. R. Lewis, M. D. Johnson, A. Xu, et al. Adenosine regulation of alveolar fluid clearance PNAS, March 6, 2007; 104(10): 4083 - 4088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. W. J. Young, C.-X. Sun, C. M. Evans, B. F. Dickey, and M. R. Blackburn A3 Adenosine Receptor Signaling Contributes to Airway Mucin Secretion after Allergen Challenge Am. J. Respir. Cell Mol. Biol., November 1, 2006; 35(5): 549 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Douillet, W. P. Robinson III, P. M. Milano, R. C. Boucher, and P. B. Rich Nucleotides induce IL-6 release from human airway epithelia via P2Y2 and p38 MAPK-dependent pathways Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L734 - L746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ryzhov, A. E. Goldstein, I. Biaggioni, and I. Feoktistov Cross-Talk between Gs- and Gq-Coupled Pathways in Regulation of Interleukin-4 by A2B Adenosine Receptors in Human Mast Cells Mol. Pharmacol., August 1, 2006; 70(2): 727 - 735. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nakano, H. Inoue, S. Fukuyama, K. Matsumoto, M. Matsumura, M. Tsuda, T. Matsumoto, H. Aizawa, and Y. Nakanishi Niflumic Acid Suppresses Interleukin-13-induced Asthma Phenotypes Am. J. Respir. Crit. Care Med., June 1, 2006; 173(11): 1216 - 1221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Chunn, A. Mohsenin, H. W. J. Young, C. G. Lee, J. A. Elias, R. E. Kellems, and M. R. Blackburn Partially adenosine deaminase-deficient mice develop pulmonary fibrosis in association with adenosine elevations Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L579 - L587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Roman, H. N. Rivera, S. Roser-Page, S. V. Sitaraman, and J. D. Ritzenthaler Adenosine induces fibronectin expression in lung epithelial cells: implications for airway remodeling Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L317 - L325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mejias, S. Chavez-Bueno, A. M. Rios, M. F. Aten, B. Raynor, E. Peromingo, P. Soni, K. D. Olsen, P. A. Kiener, A. M. Gomez, et al. Comparative Effects of Two Neutralizing Anti-Respiratory Syncytial Virus (RSV) Monoclonal Antibodies in the RSV Murine Model: Time versus Potency Antimicrob. Agents Chemother., November 1, 2005; 49(11): 4700 - 4707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Chunn, J. G. Molina, T. Mi, Y. Xia, R. E. Kellems, and M. R. Blackburn Adenosine-Dependent Pulmonary Fibrosis in Adenosine Deaminase-Deficient Mice J. Immunol., August 1, 2005; 175(3): 1937 - 1946. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ghanem, C. Lovdahl, E. Dare, C. Ledent, B. B. Fredholm, J.-M. Boeynaems, W. Van Driessche, and R. Beauwens Luminal adenosine stimulates chloride secretion through A1 receptor in mouse jejunum Am J Physiol Gastrointest Liver Physiol, May 1, 2005; 288(5): G972 - G977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. W. J. Young, J. G. Molina, D. Dimina, H. Zhong, M. Jacobson, L.-N. L. Chan, T.-S. Chan, J. J. Lee, and M. R. Blackburn A3 Adenosine Receptor Signaling Contributes to Airway Inflammation and Mucus Production in Adenosine Deaminase-Deficient Mice J. Immunol., July 15, 2004; 173(2): 1380 - 1389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ryzhov, A. E. Goldstein, A. Matafonov, D. Zeng, I. Biaggioni, and I. Feoktistov Adenosine-Activated Mast Cells Induce IgE Synthesis by B Lymphocytes: An A2B-Mediated Process Involving Th2 Cytokines IL-4 and IL-13 with Implications for Asthma J. Immunol., June 15, 2004; 172(12): 7726 - 7733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Archer, J. L. H. Cramton, J. C. Pfau, G. Colasurdo, and A. Holian Airway responsiveness after acute exposure to urban particulate matter 1648 in a DO11.10 murine model Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L337 - L343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Banerjee, H. W. J. Young, A. Barczak, D. J. Erle, and M. R. Blackburn Abnormal Alveolar Development Associated with Elevated Adenine Nucleosides Am. J. Respir. Cell Mol. Biol., January 1, 2004; 30(1): 38 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. H. Neemeth, S. J. Leibovich, E. A. Deitch, E. S. Vizi, C. Szabo, and G. Hasko cDNA Microarray Analysis Reveals a Nuclear Factor-{kappa}B-Independent Regulation of Macrophage Function by Adenosine J. Pharmacol. Exp. Ther., September 1, 2003; 306(3): 1042 - 1049. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhong, S. G. Shlykov, J. G. Molina, B. M. Sanborn, M. A. Jacobson, S. L. Tilley, and M. R. Blackburn Activation of Murine Lung Mast Cells by the Adenosine A3 Receptor J. Immunol., July 1, 2003; 171(1): 338 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fan, W. Qin, and S. J. Mustafa Characterization of adenosine receptor(s) involved in adenosine-induced bronchoconstriction in an allergic mouse model Am J Physiol Lung Cell Mol Physiol, June 1, 2003; 284(6): L1012 - L1019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Elias, T. Zheng, C. G. Lee, R. J. Homer, Q. Chen, B. Ma, M. Blackburn, and Z. Zhu Transgenic Modeling of Interleukin-13 in the Lung Chest, March 1, 2003; 123 (2009): 339S - 345S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Khan, O. Elidemir, C. E. Epstein, K. P. Lally, H. Xue, M. Blackburn, G. L. Larsen, and G. N. Colasurdo Meconium aspiration produces airway hyperresponsiveness and eosinophilic inflammation in a murine model Am J Physiol Lung Cell Mol Physiol, October 1, 2002; 283(4): L785 - L790. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Polosa Adenosine-receptor subtypes: their relevance to adenosine-mediated responses in asthma and chronic obstructive pulmonary disease Eur. Respir. J., August 1, 2002; 20(2): 488 - 496. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
