M2b macrophages reduce early reperfusion injury after myocardial ischemia in mice: A predominant role of inhibiting apoptosis via A20
M2b macrophages reduce early reperfusion injury after myocardial ischemia in mice: A predominant role of inhibiting apoptosis via A20
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M2b 巨噬细胞减少小鼠心肌缺血后早期再灌注损伤：通过 A20 抑制细胞凋亡的主要作用
DOI：
10.1016/j.ijcard.2017.07.085
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发表时间：
2017-10-15
影响因子：
3.5
通讯作者：
Wu, Zhongkai
中科院分区：
文献类型：
--
作者：
Yue, Yuan;Yang, Xiao;Wu, Zhongkai
背景：单核细胞或巨噬细胞已被评估为改善心肌缺血性疾病的潜在治疗方法，但结果一直存在争议。作为调节性巨噬细胞，M2b巨噬细胞可能具有增强的保护作用。我们验证了M2b巨噬细胞移植可以改善心肌缺血/再灌注（I/R）损伤的假设。并对其潜在机制进行了探讨。方法：用C57BL/6小鼠骨髓源性巨噬细胞脂多糖（LPS）和免疫复合物（IC）极化M2b巨噬细胞。它们是根据表面标记表达和细胞因子产生来鉴定的。用同一品系小鼠建立心肌I/R损伤模型。一旦确定缺血区，在缺血区注射1 × 10(5)个M2b巨噬细胞（MT组）或等量生理盐水（CK组）。假手术（SO）组小鼠不结扎冠状动脉。结果：我们发现MT组心肌再灌注2 h后血清肌钙蛋白I （cTnI）水平、梗死面积、细胞凋亡指数、核因子κ B （nf - κ B）信号激活显著降低；I/R引起的变化。此外，损伤导致A20的表达显著上调，并被移植的M2b巨噬细胞继续改善。结论：M2b巨噬细胞可明显减轻心肌I/R损伤。A20可能通过限制NF-kappa B信号介导的细胞凋亡参与保护机制。(C) 2017年作者。爱思唯尔爱尔兰有限公司出版。这是一篇基于CC BY-NC-ND许可（http://creativecommons.org/licenses/by-nc-nd/4.0/）的开放获取文章。
Background: Monocytes 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.Methods: M2b 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 x 10(5) 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.Results: We found a significant decrease in serum cardiac troponin I (cTnI) level, the infarct area, apoptosis index, and nuclear factor-kappa B (NF-kappa B) signaling activation in the MT group after 2 h 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.Conclusions: The administration of M2b macrophages significantly attenuated myocardial I/R injury. A20 may be part of the protective mechanism through limiting NF-kappa B signaling-mediated apoptosis. (C) 2017 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).