| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Thayer, Molly Eltzschig, Holger K. Walker, Lori Koeppen, Michael Gobel, Merit Harter, Patrick N. Bonney, Stephanie Mittelbronn, Michel Seo, Seong-wook Ravid, Katya Eckle, Tobias |
| Description |
Author Affiliation: Seo SW ( Department of Anesthesiology, University of Colorado Denver, Aurora, CO 80045); Koeppen M ( Department of Anesthesiology, University of Colorado Denver, Aurora, CO 80045); Bonney S ( Department of Anesthesiology, University of Colorado Denver, Aurora, CO 80045); Gobel M ( Department of Anesthesiology, University of Colorado Denver, Aurora, CO 80045); Thayer M ( Department of Anesthesiology, University of Colorado Denver, Aurora, CO 80045); Harter PN ( Institute of Neurology (Edinger Institute), University of Frankfurt, 60528 Frankfurt, Germany); Ravid K ( Department of Medicine, Boston University School of Medicine, Boston, MA 02118); Eltzschig HK ( Department of Anesthesiology, University of Colorado Denver, Aurora, CO 80045); Mittelbronn M ( Institute of Neurology (Edinger Institute), University of Frankfurt, 60528 Frankfurt, Germany); Walker L ( Division of Cardiology, University of Colorado Denver, Aurora, CO 80045.); Eckle T ( Department of Anesthesiology, University of Colorado Denver, Aurora, CO 80045) |
| Abstract |
The adenosine A2b receptor (Adora2b) has been implicated in cardioprotection from myocardial ischemia. As such, Adora2b was found to be critical in ischemic preconditioning (IP) or ischemia/reperfusion (IR) injury of the heart. Whereas Adora2b is present on various cells types, the tissue-specific role of Adora2b in cardioprotection is still unknown. To study the tissue-specific role of Adora2b signaling on inflammatory cells, endothelia, or myocytes during myocardial ischemia in vivo, we intercrossed floxed Adora2b mice with Lyz2-Cre(+), VE-cadherin-Cre(+), or myosin-Cre(+) transgenic mice, respectively. Mice were exposed to 60 min of myocardial ischemia with or without IP (four times for 5 min) followed by 120 min of reperfusion. Cardioprotection by IP was abolished in Adora2b(f/f)-VE-cadherin-Cre(+) or Adora2b(f/f)-myosin-Cre(+), indicating that Adora2b signaling on endothelia or myocytes mediates IP. In contrast, primarily Adora2b signaling on inflammatory cells was necessary to provide cardioprotection in IR injury, indicated by significantly larger infarcts and higher troponin levels in Adora2b(f/f)-Lyz2-Cre(+) mice only. Cytokine profiling of IR injury in Adora2b(f/f)-Lyz2-Cre(+) mice pointed toward polymorphonuclear neutrophils (PMNs). Analysis of PMNs from Adora2b(f/f)-Lyz2-Cre(+) confirmed PMNs as one source of identified tissue cytokines. Finally, adoptive transfer of Adora2b(-/-) PMNs revealed a critical role of Adora2b on PMNs in cardioprotection from IR injury. Adora2b signaling mediates different types of cardioprotection in a tissue-specific manner. These findings have implications for the use of Adora2b agonists in the treatment or prevention of myocardial injury by ischemia. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1402288 |
| Journal |
The Journal of Immunology |
| Issue Number |
4 |
| Volume Number |
195 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2015-08-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Gene Expression Regulation Receptor, Adenosine A2b Genetics Metabolism Adoptive Transfer Animals Bone Marrow Cells Disease Models, Animal Endothelium Gene Deletion Ischemic Preconditioning, Myocardial Mice Mice, Knockout Myocardial Reperfusion Injury Pathology Myocytes, Cardiac Neutrophils Immunology Organ Specificity Signal Transduction Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
