A2B Receptors on Hematopoietic Cells Control Accumulation of Dendritic Cells after Myocardial Infarction

Abstract

Dendritic cells (DC) can initiate immune reactions contributing to myocardial damage and remodeling after acute myocardial infarction (AMI). Interstitial adenosine is elevated in ischemia. We have previously shown that A2B adenosine receptors attenuate DC generation from myeloid precursors. In this study we tested the hypothesis that A2B adenosine receptors on hematopoietic cells control DC accumulation after AMI. After lethal irradiation of wild type (WT) mice, we performed bone marrow transplantations from A2B receptor knockout (KO) and from WT mice to create A2BKO‐WT chimeras and WT‐WT control, respectively. After confirming that A2BKO‐WT had greater than 90% of the hematopoietic cells replaced by week 8, AMI was created by permanent ligation of the left anterior descending coronary artery. Flow cytometry analysis on day 7 after AMI revealed significantly greater accumulation of cardiac CD11c+MHCIIhigh DC in the hearts of A2BKO‐WT chimeric mice compared with WT‐WT animals (35.0 ± 4.7 and 18.3 ± 2.1 × 103 cell/heart, respectively, p<0.05). The number of DC in the hearts of sham‐operated A2BKO‐WT and WT‐WT mice was virtually the same (2.5 ± 1.7 and 3.2 ± 1.0 × 103 cell/heart, respectively). We conclude that activation of A2B adenosine receptors on hematopoietic cells significantly attenuates AMI‐induced accumulation of CD11c+MHCIIhigh DC in the heart. Support: R01HL095787 and R01CA138923.