心肌梗塞
内科学
免疫印迹
M2巨噬细胞
人口
医学
心脏病学
结扎
嗜酸性粒细胞
白细胞介素
梗塞
心力衰竭
心功能曲线
巨噬细胞
射血分数
免疫学
男科
生物
细胞因子
体外
哮喘
基因
环境卫生
生物化学
作者
Jun Yan Xu,Yuyan Xiong,Ruijie Tang,Wenyang Jiang,Ning Yu,Zhaoting Gong,Peisen Huang,Gui‐Hao Chen,Jun Xu,Chun Xiao Wu,Mengjin Hu,Jing Xu,Yi Xu,Changjin Huang,Chen Jin,Lu Xianghua,Hai Yan Qian,Xiang Dong Li,Yuejin Yang
出处
期刊:Cardiovascular Research
[Oxford University Press]
日期:2021-07-14
卷期号:118 (9): 2165-2178
被引量:32
摘要
Abstract Aims Interleukin (IL)-5 mediates the development of eosinophils (EOS) that are essential for tissue post-injury repair. It remains unknown whether IL-5 plays a role in heart repair after myocardial infarction (MI). This study aims to test whether IL-5-induced EOS population promotes the healing and repair process post-MI and to reveal the underlying mechanisms. Methods and results MI was induced by permanent ligation of the left anterior descending coronary artery in wild-type C57BL/6 mice. Western blot and real-time polymerase chain reaction revealed elevated expression of IL-5 in the heart at 5 days post-MI. Immunohistostaining indicated that IL-5 was secreted mainly from macrophages and CD127+ cells in the setting of experimental MI. External supply of recombinant mouse IL-5 (20 min, 1 day, and 2 days after MI surgery) reduced the infarct size and increased ejection fraction and angiogenesis in the border zone. A significant expansion of EOS was detected in both the peripheral blood and infarcted myocardium after IL-5 administration. Pharmacological depletion of EOS by TRFK5 pretreatment muted the beneficial effects of IL-5 in MI mice. Mechanistic studies demonstrated that IL-5 increased the accumulation of CD206+ macrophages in infarcted myocardium at 7 days post-MI. In vitro co-culture experiments showed that EOS shifted bone marrow-derived macrophage polarization towards the CD206+ phenotypes. This activity of EOS was abolished by IL-4 neutralizing antibody, but not IL-10 or IL-13 neutralization. Western blot analyses demonstrated that EOS promoted the macrophage downstream signal transducer and activator of transcription 6 (STAT6) phosphorylation. Conclusion IL-5 facilitates the recovery of cardiac dysfunction post-MI by promoting EOS accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis.
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