Background Adenosine is produced in response to ischemia or inflammation and protects tissues from injury. Four adenosine receptors are critical in the physiologic negative-feedback mechanism for limitation and termination of tissue-specific and systemic inflammatory responses. Accumulating evidence has focused on the anti-inflammatory and immunosuppressive role of the adenosine 2A receptor (A2AR), and we have previously reported on its role in the development of bronchiolitis obliterans (BO) after lung transplantation. Few studies, however, have reported the role of the adenosine 2B receptor (A 2BR) in BO. Data suggests that the A2BR has pro-inflammatory and pro-fibrotic roles. We hypothesized that adenosine signaling through A2BR is involved in the development of BO. Methods A murine heterotopic tracheal model across a total alloantigenic mismatch was used to study A2BR signaling in BO. Tracheal transplants consisted of Balb/c donor tracheas transplanted into wild-type or A2BR knockout (KO) C57BL/6 recipients. Transplanted tracheas were removed 3, 7, 12, and 21 days after transplantation. The luminal obliteration was evaluated through hematoxylin and eosin staining, and the cellular infiltration (macrophage, neutrophil, CD3+ and Foxp3+ regulatory T cell) was detected by immunohistochemical staining. Results Compared with allografts in wild-type recipients, tracheas transplanted into A2BR KO mice displayed less BO development on Day 21. A2BR KO mice had an increase in CD3+ T cells and CD4+/CD25+/Foxp3+ regulatory T cells than did wild-type mice on Day 7. By Day 12, more CD3+ T cells were present in the wild-type trachea compared with the A2BR KO, but the percentage of CD4+/CD25+/Foxp3+ regulatory T cells remained higher in the tracheas of A2BR KO mice. Conclusions A2BR stimulation may promote the development of BO by inhibiting CD4+/CD25+/Foxp3+ regulatory T-cell infiltration.
- adenosine 2B receptor
- bronchiolitis obliterans
- lung injury
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine