Enhanced airway inflammation and remodeling in adenosine deaminase-deficient mice lacking the A2B adenosine receptor

Yang Zhou, Amir Mohsenin, E. Morschl, Hays W J Young, Jose G. Molina, Wenbin Ma, Chun Xiao Sun, Hector Martinez-Valdez, Michael R. Blackburn

Research output: Contribution to journalArticle

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Abstract

Adenosine is a signaling nucleoside that is generated in response to cellular injury and orchestrates the balance between tissue protection and the progression to pathological tissue remodeling. Adenosine deaminase (ADA)-deficient mice develop progressive airway inflammation and remodeling in association with adenosine elevations, suggesting that adenosine can promote features of chronic lung disease. Furthermore, pharmacological studies in ADA-deficient mice demonstrate that A2BR antagonism can attenuate features of chronic lung disease, implicating this receptor in the progression of chronic lung disease. This study examines the contribution of A2BR signaling in this model by generating ADA/A2BR double-knockout mice. Our hypothesis was that genetic removal of the A2BR from ADA-deficient mice would lead to diminished pulmonary inflammation and damage. Unexpectedly, ADA/A2BR double-knockout mice exhibited enhanced pulmonary inflammation and airway destruction. Marked loss of pulmonary barrier function and excessive airway neutrophilia are thought to contribute to the enhanced tissue damage observed. These findings support an important protective role for A2BR signaling during acute stages of lung disease.

Original languageEnglish
Pages (from-to)8037-8046
Number of pages10
JournalJournal of Immunology
Volume182
Issue number12
DOIs
Publication statusPublished - Jun 15 2009

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Adenosine A2B Receptors
Airway Remodeling
Lung Diseases
Adenosine
Inflammation
Adenosine Deaminase
Chronic Disease
Knockout Mice
Pneumonia
Nucleosides
Pharmacology
Lung
Mouse Ada protein
Wounds and Injuries

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Enhanced airway inflammation and remodeling in adenosine deaminase-deficient mice lacking the A2B adenosine receptor. / Zhou, Yang; Mohsenin, Amir; Morschl, E.; Young, Hays W J; Molina, Jose G.; Ma, Wenbin; Sun, Chun Xiao; Martinez-Valdez, Hector; Blackburn, Michael R.

In: Journal of Immunology, Vol. 182, No. 12, 15.06.2009, p. 8037-8046.

Research output: Contribution to journalArticle

Zhou, Y, Mohsenin, A, Morschl, E, Young, HWJ, Molina, JG, Ma, W, Sun, CX, Martinez-Valdez, H & Blackburn, MR 2009, 'Enhanced airway inflammation and remodeling in adenosine deaminase-deficient mice lacking the A2B adenosine receptor', Journal of Immunology, vol. 182, no. 12, pp. 8037-8046. https://doi.org/10.4049/jimmunol.0900515
Zhou, Yang ; Mohsenin, Amir ; Morschl, E. ; Young, Hays W J ; Molina, Jose G. ; Ma, Wenbin ; Sun, Chun Xiao ; Martinez-Valdez, Hector ; Blackburn, Michael R. / Enhanced airway inflammation and remodeling in adenosine deaminase-deficient mice lacking the A2B adenosine receptor. In: Journal of Immunology. 2009 ; Vol. 182, No. 12. pp. 8037-8046.
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