Enhanced airway inflammation and remodeling in adenosine deaminase-deficient mice lacking the A2B adenosine receptor.
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 A(2B)R antagonism can attenuate features of chronic lung disease, implicating this receptor in the progression of chronic lung disease. This study examines the contribution of A(2B)R signaling in this model by generating ADA/A(2B)R double-knockout mice. Our hypothesis was that genetic removal of the A(2B)R from ADA-deficient mice would lead to diminished pulmonary inflammation and damage. Unexpectedly, ADA/A(2B)R 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 A(2B)R signaling during acute stages of lung disease.
Zhou
Yang
Y
Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, TX 77030, USA.
Mohsenin
Amir
A
Morschl
Eva
E
Young
Hays W J
HW
Molina
Jose G
JG
Ma
Wenbin
W
Sun
Chun-Xiao
CX
Martinez-Valdez
Hector
H
Blackburn
Michael R
MR
D000243:Adenosine Deaminase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003094:Collagen / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D043704:Receptor, Adenosine A2B / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D016207:Cytokines; D043704:Receptor, Adenosine A2B; D003094:Collagen; D000243:Adenosine Deaminase