Resident Cardiac Immune Cells and Expression of the Ectonucleotidase Enzymes CD39 and CD73 after Ischemic Injury

Abstract

BackgroundThe ectoenzymes CD39 and CD73 are expressed by a broad range of immune cells and promote the extracellular degradation of nucleotides to anti-inflammatory adenosine. This study explored the abundance of CD73 and CD39 on circulating and resident cardiac leukocytes and coronary endothelial cells under control conditions and in response to inflammation following myocardial ischemia and reperfusion (I/R).Methods and ResultsA method was elaborated to permit FACS analysis of non-myocardial cells (resident leukocytes, coronary endothelium and CD31− CD45− cells) of the unstressed heart. Under control conditions the murine heart contained 2.3×103 resident leukocytes/mg tissue, the most prominent fraction being antigen-presenting mononuclear cells (CD11b+ CD11c+ F4/80+ MHCII+) followed by B-cells, monocytes and T-cells. CD73 was highly expressed on circulating and resident cardiac lymphoid cells with little expression on myeloid cells, while the opposite was true for CD39. Cardiomyocytes and erythrocytes do not measurably express CD39/CD73 and CD39 dominates on coronary endothelium. Three days after I/R, CD73 was significantly upregulated on invading granulocytes (2.8-fold) and T-cells (1.5-fold). Compared with coronary endothelial cells, CD73 associated with leukocytes comprised 2/3 of the total cardiac CD73.ConclusionOur study suggests that extracellular ATP formed during I/R is preferentially degraded by CD39 present on myeloid cells, while the formation of immunosuppressive adenosine is mainly catalysed by CD73 present on granulocytes and lymphoid cells. Upregulated CD73 on granulocytes and T-cells infiltrating the injured heart is consistent with the existence of an autocrine adenosinergic loop which may promote the healing process.

CR1-mediated ATP Release by Human Red Blood Cells Promotes CR1 Clustering and Modulates the Immune Transfer Process

“…1C). These results are in full agreement with a recent finding that human RBC do not express detectable levels of the ecto-ATPase CD39/NTPDase2 (18). Therefore, ARL 67156 was not used in any subsequent experiments.…”

Myocardial aging as a T-cell–mediated phenomenon

“…Recent studies indicated that the murine myocardium harbors abundant tissueresident macrophages and bona fide dendritic cells in the steady state (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). In the present study, we observed that a small population of B and T lymphocytes can also be consistently found in the myocardial parenchyma of healthy mice.…”

“…myocardial | aging | T cells | inflammation | inflammaging T he myocardial cellular composition has been revisited in recent years, and leukocyte subsets residing in the healthy heart have been described (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Cardiac-resident macrophages exhibiting an M2-like gene expression profile were found to be distributed in close association with the coronary vascular bed (3), and niches for dendritic cells (CD11c + MHC-II high CD80/86 low ) were found near the cardiac valves of the intact heart (1).…”

CD73 Inhibition Shifts Cardiac Macrophage Polarization toward a Microbicidal Phenotype and Ameliorates the Outcome of Experimental Chagas Cardiomyopathy

“…Postinfection, the influx of immune cells consumes large quantities of oxygen, and ischemic cells rapidly respond to the hypoxic and inflammatory environment by releasing ATP (normally present within cardiomyocytes in millimolar concentrations) (13,14). Once released, the ATP is converted to ADP/AMP and then to ADO by the ectonucleoside triphosphate diphosphohydrolase-1 (CD39) and the ecto-5'-nucleotidase (CD73), respectively.…”