M2b macrophages reduce early reperfusion injury after myocardial ischemia in mice: A predominant role of inhibiting apoptosis via A20

Abstract

BackgroundMonocytes or macrophages have been assessed as potential therapeutics to ameliorate myocardial ischemic diseases, but the results have been controversial. As regulatory macrophages, M2b macrophages could have enhanced protective effects. We tested the hypothesis that transplantation of M2b macrophages could ameliorate myocardial ischemia/reperfusion (I/R) injury. The potential mechanisms involved in it were investigated. MethodsM2b macrophages were polarized by lipopolysaccharide (LPS) and the immune complex (IC) from bone marrow-derived macrophages (BMDMs) of C57BL/6 mice. They were identified based on surface marker expression and cytokine production. Myocardial I/R injury models were established with the same strain of mice. Once the ischemic area was identified, either 1×105 M2b macrophages (MT group) or the same volume of normal saline (CK group) was injected into the ischemic zone. Mice in the sham operation (SO) group underwent the operation without ligation of the coronary artery. ResultsWe found a significant decrease in serum cardiac troponin I (cTnI) level, the infarct area, apoptosis index, and nuclear factor-κB (NF-κB) signaling activation in the MT group after 2h of reperfusion; the changes were induced by I/R. In addition, the injury resulted in significantly up-regulated expression of A20 and continued to be improved by the transplanted M2b macrophages. ConclusionsThe administration of M2b macrophages significantly attenuated myocardial I/R injury. A20 may be part of the protective mechanism through limiting NF-κB signaling-mediated apoptosis.