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Acta Physiologica 2012; Volume 204, Supplement 689
91st Annual Meeting of The German Physiological Society
3/22/2012-3/25/2012
Dresden, Germany
ROLE OF CD73 IN CARDIAC HEALING AFTER ISCHEMIA/REPERFUSION
Abstract number: P104
Borg1 *N., Bonner1 F., Flogel1 U., Jacoby1 C., Burghoff2 S., Schrader1 J.
1Heinrich-Heine-Universitt Dsseldorf, Institut fr molekulare Kardiologie, Dsseldorf, Germany
2Martin-Luther-Universitt Halle-Wittenberg, Institut fr Humangenetik und medizinische Biologie, Halle/Saale, Germany
CD39 and CD73 are ectoenzymes expressed on immune cells catalysing the extracellular degradation of ATP to adenosine. We analysed the expression of both ectoenzymes on cardiac leukocytes under basal conditions and after ischemia/reperfusion (I/R) and performed functional measurements in CD73-/- mice to investigate the role of adenosine in cardiac healing.
Immune cells were isolated from myocardial tissue after collagenase digestion. The abundance of leukocytes and the expression pattern of CD39 and CD73 were analyzed by flow cytometry after I/R (50 min occlusion). Ejection fraction was measured by MRI.
The unstressed murine heart contained 2.3x 103 resident leukocytes/mg tissue. CD73 was highly expressed on cardiac lymphoid cells with little expression on myeloid cells, whereas the opposite was true for CD39. Three days after I/R, CD73 was significantly upregulated on invading granulocytes (2.8-fold) and T-cells (1.5-fold). CD73-/- mutants (KO) showed a significantly reduced ejection fraction (EF) after I/R (day 28 after I/R: WT: 51.99 ± 2,55%; KO: 36.16 ± 7.4%; n = 5; p<0.01). Concomitantly, immune cells persisted in cardiac tissue (day 14 after I/R: WT: 2.91 ± 1.18; KO: 9.36 ± 3.71 x 103 leukocytes/ mg heart tissue; p<0.05). Transplantation of WT-bone marrow into KO fully restored the WT phenotype (EF: WT®WT 55.72 ± 8.11%; WT®KO 59.23 ± 13.87%; p<0.05).
Our findings suggest enhanced localized formation of anti-inflammatory adenosine on infiltrating leukocytes after I/R. If CD73-derived adenosine is lacking, the inflammatory response is prolonged implying an important role of adenosine in the healing process after I/R.
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Acta Physiologica 2012; Volume 204, Supplement 689 :P104